Table Info

Table 2.

SPECT radioactive pharmaceuticals and their clinical uses

Tracers	Half-life	Target	MOA	Clinical use	References
123I-IMP	13.3 h	rCBF	Lipophilic tracer crosses BBB, binds to brain tissue in proportion to perfusion	Diagnosis of dementia, including AD	[139, 140]
99mTc-HMPAO	6.7 h	rCBF	Lipophilic tracer crosses the BBB, gets trapped in neurons, and reflects cerebral perfusion	Diagnosis and evaluation of AD, monitoring disease progression, and treatment response	[141]
99mTc-ECD	6 h	rCBF	Bind to brain tissue, reflecting rCBF	Evaluating cerebral perfusion, distinguishing AD from other dementias	[142–144]
123I-AV-45	110 min	Aβ plaques	Binds to Aβ aggregates in the brain	Used to assess the presence of Aβ in AD	[68]
123I-PiB	13.3 h	Aβ plaques, tau protein	Amyloid-binding, PET-SPECT hybrid	Diagnosis of AD, differentiating AD from other dementias	[125, 145]
Benzathine (99mTc-Tc-BZ)	6.3 h	Aβ plaques, BBB disruption	BBB disruption, SPECT-imaging of brain function and perfusion	Diagnosis of AD, monitoring disease progression, and treatment response	[146]

123I-IMP: iodine-123 labeled 2-iodo-3-(N,N-dimethylamino) propylamine; 99mTc-HMPAO: technetium-99m hexamethylpropyleneamine oxime; 99mTc-ECD: technetium-99m ethyl cysteinate dimer; 123I-AV-45: iodine-123 amyvid (florbetapir); 123I-PiB: iodine-123 pittsburgh compound B; rCBF: regional cerebral blood flow; Aβ: amyloid beta; BBB: blood brain barrier; SPECT: single photon emission computed tomography; PET: positron emission tomography; AD: Alzheimer’s disease; MOA: mechanism of action

Declarations

Acknowledgments

We acknowledge the support of the Department of Nuclear Medicine at Nanjing First Hospital.

Author contributions

JM: Writing—original draft. RD: Conceptualization, Writing—review & editing. BL: Writing—review & editing. JW: Writing—review & editing. MS: Writing—review & editing. FW: Conceptualization, Supervision, Writing—review & editing, Funding acquisition. YY: Conceptualization, Investigation, Writing—review & editing.

Conflicts of interest

The authors declare that they have no conflicts of interest.

Ethical approval

Not applicable.

Consent to participate

Not applicable.

Consent to publication

Not applicable.

Availability of data and materials

Not applicable.

Funding

This work is supported by the National Key Research and Development Program of China [2022YFC2406900]; the Key subjects of nuclear medicine: Jiangsu Provincial Institute of Medical Sciences [JSDW202247]; Jiangsu Provincial Medical Key Discipline Cultivation Unit [JSDW202247]; Nanjing International/Hong Kong, Macao, and Taiwan Science and Technology Cooperation Program Project [202308005]; the National Natural Science Foundation of China [82301609]; China Postdoctoral Science Foundation [2022M711666]; Natural Science Foundation of Jiangsu Province [BK20220196]; the International Joint Research and Development Project of Nanjing [202201030]; the International Joint Research and Development Project of Nanjing [202308005]. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.

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References

Lin KJ, Hsu WC, Hsiao IT, Wey SP, Jin LW, Skovronsky D, et al. Whole-body biodistribution and brain PET imaging with [18F]AV-45, a novel amyloid imaging agent--a pilot study. Nucl Med Biol. 2010;37:497–508. [DOI] [PubMed]

Liu Y, Zhu L, Plössl K, Choi SR, Qiao H, Sun X, et al. Optimization of automated radiosynthesis of [¹⁸F]-AV-45: a new PET imaging agent for Alzheimer’s disease. Nucl Med Biol. 2010;37:917–25. [DOI]

Rodrigue KM, Kennedy KM, Park DC. Beta-amyloid deposition and the aging brain. Neuropsychol Rev. 2009;19:436–50. [DOI] [PubMed] [PMC]

Pike V. Overview of clinically available radiotracers for imaging in neurodegenerative disorders. In: Cross DJ, Mosci K, Minoshima S, editors. Molecular imaging of neurodegenerative disorders. Cham: Springer International Publishing; 2023. pp. 35–55. [DOI]

Hall B, Mak E, Cervenka S, Aigbirhio FI, Rowe JB, O’Brien JT. In vivo tau PET imaging in dementia: Pathophysiology, radiotracer quantification, and a systematic review of clinical findings. Ageing Res Rev. 2017;36:50–63. [DOI]

Tahami Monfared AA, Byrnes MJ, White LA, Zhang Q. Alzheimer’s Disease: Epidemiology and Clinical Progression. Neurol Ther. 2022;11:553–69. [DOI] [PubMed] [PMC]

Korczyn AD, Grinberg LT. Is Alzheimer disease a disease? Nat Rev Neurol. 2024;20:245–51. [DOI] [PubMed]

Breijyeh Z, Karaman R. Comprehensive Review on Alzheimer’s Disease: Causes and Treatment. Molecules. 2020;25:5789. [DOI] [PubMed] [PMC]

Jack CR Jr, Bennett DA, Blennow K, Carrillo MC, Dunn B, Haeberlein SB, et al.; Contributors. NIA-AA Research Framework: Toward a biological definition of Alzheimer’s disease. Alzheimers Dement. 2018;14:535–62. [DOI] [PubMed] [PMC]

10.

Rostagno AA. Pathogenesis of Alzheimer’s Disease. Int J Mol Sci. 2022;24:107. [DOI] [PubMed] [PMC]

11.

Wen X, Huang C, Xie H, Hu D, Luo J, Li K. The applications of CircRNA in the diagnosis and treatment of Alzheimer’s disease. Mol Neurobiol. 2024;61:6501–10. [DOI]

12.

Castellani RJ, Plascencia-Villa G, Perry G. Pathogenesis of Alzheimer’s disease. In: Kostrzewa RM, editor. Handbook of Neurotoxicity. Springer, Cham; 2021. pp. 1–20. [DOI]

13.

Chen Y, Yu Y. Tau and neuroinflammation in Alzheimer’s disease: interplay mechanisms and clinical translation. J Neuroinflammation. 2023;20:165. [DOI] [PubMed] [PMC]

14.

Guo T, Zhang D, Zeng Y, Huang TY, Xu H, Zhao Y. Molecular and cellular mechanisms underlying the pathogenesis of Alzheimer’s disease. Mol Neurodegener. 2020;15:40. [DOI] [PubMed] [PMC]

15.

Kolarova M, García-Sierra F, Bartos A, Ricny J, Ripova D. Structure and pathology of tau protein in Alzheimer disease. Int J Alzheimers Dis. 2012;2012:731526. [DOI] [PubMed] [PMC]

16.

Braak H, Braak E. Neuropathological stageing of Alzheimer-related changes. Acta Neuropathol. 1991;82:239–59. [DOI] [PubMed]

17.

Onuska KM. The Dual Role of Microglia in the Progression of Alzheimer’s Disease. J Neurosci. 2020;40:1608–10. [DOI] [PubMed] [PMC]

18.

Miao J, Ma H, Yang Y, Liao Y, Lin C, Zheng J, et al. Microglia in Alzheimer’s disease: pathogenesis, mechanisms, and therapeutic potentials. Front Aging Neurosci. 2023;15:1201982. [DOI] [PubMed] [PMC]

19.

Koffie RM, Hyman BT, Spires-Jones TL. Alzheimer’s disease: synapses gone cold. Mol Neurodegener. 2011;6:63. [DOI] [PubMed] [PMC]

20.

Chen Y, Fu AKY, Ip NY. Synaptic dysfunction in Alzheimer’s disease: Mechanisms and therapeutic strategies. Pharmacol Ther. 2019;195:186–98. [DOI] [PubMed]

21.

Mangalmurti A, Lukens JR. How neurons die in Alzheimer’s disease: Implications for neuroinflammation. Curr Opin Neurobiol. 2022;75:102575. [DOI] [PubMed] [PMC]

22.

Misrani A, Tabassum S, Yang L. Mitochondrial Dysfunction and Oxidative Stress in Alzheimer’s Disease. Front Aging Neurosci. 2021;13:617588. [DOI] [PubMed] [PMC]

23.

Wang X, Wang W, Li L, Perry G, Lee HG, Zhu X. Oxidative stress and mitochondrial dysfunction in Alzheimer’s disease. Biochim Biophys Acta. 2014;1842:1240–7. [DOI] [PubMed] [PMC]

24.

Ghosh S, Ali R, Verma S. Aβ-oligomers: A potential therapeutic target for Alzheimer’s disease. Int J Biol Macromol. 2023;239:124231. [DOI] [PubMed]

25.

Gao X, Chen Q, Yao H, Tan J, Liu Z, Zhou Y, et al. Epigenetics in Alzheimer’s disease. Front Aging Neurosci. 2022;14:911635. [DOI]

26.

Stoccoro A, Coppedè F. Role of epigenetics in Alzheimer’s disease pathogenesis. Neurodegener Dis Manag. 2018;8:181–93. [DOI] [PubMed]

27.

Hayden EY, Teplow DB. Amyloid β-protein oligomers and Alzheimer’s disease. Alzheimers Res Ther. 2013;5:60. [DOI] [PubMed] [PMC]

28.

Mroczko B, Groblewska M, Litman-Zawadzka A, Kornhuber J, Lewczuk P. Amyloid β oligomers (AβOs) in Alzheimer’s disease. J Neural Transm (Vienna). 2018;125:177–91. [DOI] [PubMed]

29.

Viola KL, Klein WL. Amyloid β oligomers in Alzheimer’s disease pathogenesis, treatment, and diagnosis. Acta Neuropathol. 2015;129:183–206. [DOI] [PubMed] [PMC]

30.

Selkoe DJ, Hardy J. The amyloid hypothesis of Alzheimer’s disease at 25 years. EMBO Mol Med. 2016;8:595–608. [DOI] [PubMed] [PMC]

31.

Baldeiras I, Santana I, Leitão MJ, Gens H, Pascoal R, Tábuas-Pereira M, et al. Addition of the Aβ42/40 ratio to the cerebrospinal fluid biomarker profile increases the predictive value for underlying Alzheimer’s disease dementia in mild cognitive impairment. Alzheimers Res Ther. 2018;10:33. [DOI] [PubMed] [PMC]

32.

Zhang H, Wei W, Zhao M, Ma L, Jiang X, Pei H, et al. Interaction between Aβ and Tau in the Pathogenesis of Alzheimer’s Disease. Int J Biol Sci. 2021;17:2181–92. [DOI] [PubMed] [PMC]

33.

Zhang H, Jiang X, Ma L, Wei W, Li Z, Chang S, et al. Role of Aβ in Alzheimer’s-related synaptic dysfunction. Front Cell Dev Biol. 2022;10:964075. [DOI] [PubMed] [PMC]

34.

Rahman MM, Lendel C. Extracellular protein components of amyloid plaques and their roles in Alzheimer’s disease pathology. Mol Neurodegener. 2021;16:59. [DOI] [PubMed] [PMC]

35.

Garbuz DG, Zatsepina OG, Evgen’ev MB. Beta amyloid, tau protein, and neuroinflammation: An attempt to integrate different hypotheses of Alzheimer’s disease pathogenesis. Mol Biol. 2021;55:670–82. [DOI]

36.

Gouras GK, Olsson TT, Hansson O. β-Amyloid peptides and amyloid plaques in Alzheimer’s disease. Neurotherapeutics. 2015;12:3–11. [DOI] [PubMed] [PMC]

37.

Hardy J, Selkoe DJ. The amyloid hypothesis of Alzheimer’s disease: progress and problems on the road to therapeutics. Science. 2002;297:353–6. [DOI] [PubMed]

38.

Yang H, Li J, Li X, Ma L, Hou M, Zhou H, et al. Based on molecular structures: Amyloid-β generation, clearance, toxicity and therapeutic strategies. Front Mol Neurosci. 2022;15:927530. [DOI] [PubMed] [PMC]

39.

Cai W, Li L, Sang S, Pan X, Zhong C. Physiological Roles of β-amyloid in Regulating Synaptic Function: Implications for AD Pathophysiology. Neurosci Bull. 2023;39:1289–308. [DOI] [PubMed] [PMC]

40.

Cole SL, Vassar R. The Alzheimer’s disease beta-secretase enzyme, BACE1. Mol Neurodegener. 2007;2:22. [DOI] [PubMed] [PMC]

41.

Zhang L, Liang X, Zhang Z, Luo H. Cerebrospinal fluid and blood biomarkers in the diagnostic assays of Alzheimer’s disease. J Innovative Opt Health Sci. 2022;15:2230001. [DOI]

42.

Medeiros R, Baglietto-Vargas D, LaFerla FM. The role of tau in Alzheimer’s disease and related disorders. CNS Neurosci Ther. 2011;17:514–24. [DOI] [PubMed] [PMC]

43.

Gu JL, Liu F. Tau in Alzheimer’s Disease: Pathological Alterations and an Attractive Therapeutic Target. Curr Med Sci. 2020;40:1009–21. [DOI] [PubMed]

44.

Šimić G, Babić Leko M, Wray S, Harrington C, Delalle I, Jovanov-Milošević N, et al. Tau Protein Hyperphosphorylation and Aggregation in Alzheimer’s Disease and Other Tauopathies, and Possible Neuroprotective Strategies. Biomolecules. 2016;6:6. [DOI] [PubMed] [PMC]

45.

von Bergen M, Friedhoff P, Biernat J, Heberle J, Mandelkow EM, Mandelkow E. Assembly of tau protein into Alzheimer paired helical filaments depends on a local sequence motif ((306)VQIVYK(311)) forming beta structure. Proc Natl Acad Sci U S A. 2000;97:5129–34. [DOI] [PubMed] [PMC]

46.

Braak H, Braak E. Staging of Alzheimer’s disease-related neurofibrillary changes. Neurobiol Aging. 1995;16:271–8. [DOI] [PubMed]

47.

Nelson PT, Braak H, Markesbery WR. Neuropathology and cognitive impairment in Alzheimer disease: a complex but coherent relationship. J Neuropathol Exp Neurol. 2009;68:1–14. [DOI] [PubMed] [PMC]

48.

Braak H, Braak E, Grundke-Iqbal I, Iqbal K. Occurrence of neuropil threads in the senile human brain and in Alzheimer’s disease: a third location of paired helical filaments outside of neurofibrillary tangles and neuritic plaques. Neurosci Lett. 1986;65:351–5. [DOI] [PubMed]

49.

Kayed R, Head E, Sarsoza F, Saing T, Cotman CW, Necula M, et al. Fibril specific, conformation dependent antibodies recognize a generic epitope common to amyloid fibrils and fibrillar oligomers that is absent in prefibrillar oligomers. Mol Neurodegener. 2007;2:18. [DOI] [PubMed] [PMC]

50.

Grover A, Houlden H, Baker M, Adamson J, Lewis J, Prihar G, et al. 5’ splice site mutations in tau associated with the inherited dementia FTDP-17 affect a stem-loop structure that regulates alternative splicing of exon 10. J Biol Chem. 1999;274:15134–43. [DOI] [PubMed]

51.

Cruts M, Gijselinck I, van der Zee J, Engelborghs S, Wils H, Pirici D, et al. Null mutations in progranulin cause ubiquitin-positive frontotemporal dementia linked to chromosome 17q21. Nature. 2006;442:920–4. [DOI] [PubMed]

52.

Heneka MT, Carson MJ, El Khoury J, Landreth GE, Brosseron F, Feinstein DL, et al. Neuroinflammation in Alzheimer’s disease. Lancet Neurol. 2015;14:388–405. [DOI] [PubMed] [PMC]

53.

Webers A, Heneka MT, Gleeson PA. The role of innate immune responses and neuroinflammation in amyloid accumulation and progression of Alzheimer’s disease. Immunol Cell Biol. 2020;98:28–41. [DOI] [PubMed]

54.

Wang WY, Tan MS, Yu JT, Tan L. Role of pro-inflammatory cytokines released from microglia in Alzheimer’s disease. Ann Transl Med. 2015;3:136. [DOI] [PubMed] [PMC]

55.

Hansen DV, Hanson JE, Sheng M. Microglia in Alzheimer’s disease. J Cell Biol. 2018;217:459–72. [DOI] [PubMed] [PMC]

56.

Singh D. Astrocytic and microglial cells as the modulators of neuroinflammation in Alzheimer’s disease. J Neuroinflammation. 2022;19:206. [DOI] [PubMed] [PMC]

57.

Lawrence JM, Schardien K, Wigdahl B, Nonnemacher MR. Roles of neuropathology-associated reactive astrocytes: a systematic review. Acta Neuropathol Commun. 2023;11:42. [DOI] [PubMed] [PMC]

58.

Kiraly M, Foss JF, Giordano T. Neuroinflammation, its Role in Alzheimer’s Disease and Therapeutic Strategie. J Prev Alzheimers Dis. 2023;10:686–98. [DOI] [PubMed]

59.

Park SH, Kwon KJ, Kim MY, Kim JH, Moon WJ, Ryu HJ, et al.; K-ARPI. Diagnostic Tools for Alzheimer’s Disease: A Narrative Review Based on Our Own Research Experience. Dement Neurocogn Disord. 2023;22:16–27. [DOI] [PubMed] [PMC]

60.

Bhujbal SS, Kad MM, Patole VC. Recent diagnostic techniques for the detection of Alzheimer's disease: a short review. Ir J Med Sci. 2023;192:2417–26. [DOI] [PubMed]

61.

Aditya Shastry K, Sanjay HA. Artificial intelligence techniques for the effective diagnosis of Alzheimer’s disease: A review. Multimed Tools Appl. 2024;83:40057–92. [DOI]

62.

Jack CR Jr, Holtzman DM. Biomarker modeling of Alzheimer’s disease. Neuron. 2013;80:1347–58. [DOI] [PubMed] [PMC]

63.

Weller J, Budson A. Current understanding of Alzheimer’s disease diagnosis and treatment. F1000Res. 2018;7:F1000 Faculty Rev-1161. [DOI] [PubMed] [PMC]

64.

Lee JC, Kim SJ, Hong S, Kim Y. Diagnosis of Alzheimer’s disease utilizing amyloid and tau as fluid biomarkers. Exp Mol Med. 2019;51:1–10. [DOI] [PubMed] [PMC]

65.

Koriath CAM, Kenny J, Ryan NS, Rohrer JD, Schott JM, Houlden H, et al. Genetic testing in dementia - utility and clinical strategies. Nat Rev Neurol. 2021;17:23–36. [DOI] [PubMed]

66.

Mayo C. Diagnosing Alzheimer’s: How Alzheimer’s is diagnosed. Mayo Clinic; c2024 [cited 2024 Mar 13]. Available from: https://www.mayoclinic.org/diseases-conditions/alzheimers-disease/in-depth/alzheimers/art-20048075#:~:text=Laboratory%20tests,symptoms%20are%20rapidly%20getting%20worse

67.

Petersen RC, Roberts RO, Knopman DS, Boeve BF, Geda YE, Ivnik RJ, et al. Mild cognitive impairment: ten years later. Arch Neurol. 2009;66:1447–55. [DOI] [PubMed] [PMC]

68.

Blennow K, Zetterberg H. Biomarkers for Alzheimer’s disease: current status and prospects for the future. J Intern Med. 2018;284:643–63. [DOI] [PubMed]

69.

Johnson KA, Schultz A, Betensky RA, Becker JA, Sepulcre J, Rentz D, et al. Tau positron emission tomographic imaging in aging and early Alzheimer disease. Ann Neurol. 2016;79:110–9. [DOI] [PubMed] [PMC]

70.

Jack CR Jr, Knopman DS, Jagust WJ, Shaw LM, Aisen PS, Weiner MW, et al. Hypothetical model of dynamic biomarkers of the Alzheimer’s pathological cascade. Lancet Neurol. 2010;9:119–28. [DOI] [PubMed] [PMC]

71.

Convit A, De Leon MJ, Tarshish C, De Santi S, Tsui W, Rusinek H, et al. Specific hippocampal volume reductions in individuals at risk for Alzheimer’s disease. Neurobiol Aging. 1997;18:131–8. [DOI] [PubMed]

72.

Schuff N, Woerner N, Boreta L, Kornfield T, Shaw LM, Trojanowski JQ, et al.; Alzheimer’s Disease Neuroimaging Initiative. MRI of hippocampal volume loss in early Alzheimer’s disease in relation to ApoE genotype and biomarkers. Brain. 2009;132:1067–77. [DOI] [PubMed] [PMC]

73.

Nobis L, Manohar SG, Smith SM, Alfaro-Almagro F, Jenkinson M, Mackay CE, et al. Hippocampal volume across age: Nomograms derived from over 19,700 people in UK Biobank. Neuroimage Clin. 2019;23:101904. [DOI] [PubMed] [PMC]

74.

Bateman RJ, Smith J, Donohue MC, Delmar P, Abbas R, Salloway S, et al.; GRADUATE I and II Investigators and the Gantenerumab Study Group. Two Phase 3 Trials of Gantenerumab in Early Alzheimer’s Disease. N Engl J Med. 2023;389:1862–76. [DOI] [PubMed] [PMC]

75.

Tian Q, Bilgic B, Fan Q, Ngamsombat C, Zaretskaya N, Fultz NE, et al. Improving in vivo human cerebral cortical surface reconstruction using data-driven super-resolution. Cereb Cortex. 2021;31:463–82. [DOI] [PubMed] [PMC]

76.

Kehoe EG, McNulty JP, Mullins PG, Bokde AL. Advances in MRI biomarkers for the diagnosis of Alzheimer’s disease. Biomark Med. 2014;8:1151–69. [DOI] [PubMed]

77.

Apostolova LG, Dutton RA, Dinov ID, Hayashi KM, Toga AW, Cummings JL, et al. Conversion of mild cognitive impairment to Alzheimer disease predicted by hippocampal atrophy maps. Arch Neurol. 2006;63:693–9. [DOI] [PubMed]

78.

Anderson CJ, Lewis JS. Current status and future challenges for molecular imaging. Philos Trans A Math Phys Eng Sci. 2017;375:20170023. [DOI] [PubMed]

79.

Li KR, Wu AG, Tang Y, He XP, Yu CL, Wu JM, et al. The Key Role of Magnetic Resonance Imaging in the Detection of Neurodegenerative Diseases-Associated Biomarkers: A Review. Mol Neurobiol. 2022;59:5935–54. [DOI] [PubMed]

80.

Anthony M, Lin F. A Systematic Review for Functional Neuroimaging Studies of Cognitive Reserve Across the Cognitive Aging Spectrum. Arch Clin Neuropsychol. 2018;33:937–48. [DOI] [PubMed] [PMC]

81.

Scarapicchia V, Brown C, Mayo C, Gawryluk JR. Functional Magnetic Resonance Imaging and Functional Near-Infrared Spectroscopy: Insights from Combined Recording Studies. Front Hum Neurosci. 2017;11:419. [DOI] [PubMed] [PMC]

82.

Banerjee D, Muralidharan A, Hakim Mohammed AR, Malik BH. Neuroimaging in Dementia: A Brief Review. Cureus. 2020;12:e8682. [DOI] [PubMed] [PMC]

83.

Ferrando R, Damian A. Brain SPECT as a Biomarker of Neurodegeneration in Dementia in the Era of Molecular Imaging: Still a Valid Option? Front Neurol. 2021;12:629442. [DOI] [PubMed] [PMC]

84.

Chaney A, Williams SR, Boutin H. In vivo molecular imaging of neuroinflammation in Alzheimer’s disease. J Neurochem. 2019;149:438–51. [DOI] [PubMed] [PMC]

85.

Buckner RL, DiNicola LM. The brain’s default network: updated anatomy, physiology and evolving insights. Nat Rev Neurosci. 2019;20:593–608. [DOI] [PubMed]

86.

Buckner RL, Andrews-Hanna JR, Schacter DL. The Brain's Default Network: Anatomy, Function, and Relevance to Disease. Ann N Y Acad Sci. 2008;1124:1–38. [DOI]

87.

Palmer SM, Crewther SG, Carey LM; START Project Team. A meta-analysis of changes in brain activity in clinical depression. Front Hum Neurosci. 2015;8:1045. [DOI] [PubMed] [PMC]

88.

Graff-Radford J, Kantarci K. Magnetic resonance spectroscopy in Alzheimer’s disease. Neuropsychiatr Dis Treat. 2013;9:687–96. [DOI] [PubMed] [PMC]

89.

Wang H, Tan L, Wang HF, Liu Y, Yin RH, Wang WY, et al. Magnetic Resonance Spectroscopy in Alzheimer’s Disease: Systematic Review and Meta-Analysis. J Alzheimers Dis. 2015;46:1049–70. [DOI] [PubMed]

90.

Cocuzzo D, Lin A, Stanwell P, Mountford C, Keshava N. In Vivo Brain Magnetic Resonance Spectroscopy: A Measurement of Biomarker Sensitivity to Post-Processing Algorithms. IEEE J Transl Eng Health Med. 2014;2:2900117. [DOI] [PubMed] [PMC]

91.

Patel AN, Jhamandas JH. Neuronal receptors as targets for the action of amyloid-beta protein (Aβ) in the brain. Expert Rev Mol Med. 2012;14:e2. [DOI] [PubMed]

92.

Kar S, Slowikowski SP, Westaway D, Mount HT. Interactions between beta-amyloid and central cholinergic neurons: implications for Alzheimer’s disease. J Psychiatry Neurosci. 2004;29:427–41. [PubMed] [PMC]

93.

Mueller SG, Schuff N, Yaffe K, Madison C, Miller B, Weiner MW. Hippocampal atrophy patterns in mild cognitive impairment and Alzheimer’s disease. Hum Brain Mapp. 2010;31:1339–47. [DOI] [PubMed] [PMC]

94.

Raut S, Bhalerao A, Powers M, Gonzalez M, Mancuso S, Cucullo L. Hypometabolism, Alzheimer’s Disease, and Possible Therapeutic Targets: An Overview. Cells. 2023;12:2019. [DOI] [PubMed] [PMC]

95.

Mosconi L, Pupi A, De Leon MJ. Brain glucose hypometabolism and oxidative stress in preclinical Alzheimer’s disease. Ann N Y Acad Sci. 2008;1147:180–95. [DOI] [PubMed] [PMC]

96.

Kumar V, Kim SH, Bishayee K. Dysfunctional Glucose Metabolism in Alzheimer’s Disease Onset and Potential Pharmacological Interventions. Int J Mol Sci. 2022;23:9540. [DOI] [PubMed] [PMC]

97.

Panza F, Frisardi V, Imbimbo BP, Capurso C, Logroscino G, Sancarlo D, et al. REVIEW: γ-Secretase inhibitors for the treatment of Alzheimer’s disease: The current state. CNS Neurosci Ther. 2010;16:272–84. [DOI] [PubMed] [PMC]

98.

Blennow K, Hampel H, Weiner M, Zetterberg H. Cerebrospinal fluid and plasma biomarkers in Alzheimer disease. Nat Rev Neurol. 2010;6:131–44. [DOI] [PubMed]

99.

Weber DM, Tran D, Goldman SM, Taylor SW, Ginns EI, Lagier RJ, et al. High-Throughput Mass Spectrometry Assay for Quantifying β-Amyloid 40 and 42 in Cerebrospinal Fluid. Clin Chem. 2019;65:1572–80. [DOI] [PubMed]

100.

Hansson O, Batrla R, Brix B, Carrillo MC, Corradini V, Edelmayer RM, et al. The Alzheimer’s Association international guidelines for handling of cerebrospinal fluid for routine clinical measurements of amyloid β and tau. Alzheimers Dement. 2021;17:1575–82. [DOI] [PubMed]

101.

Visser PJ, Reus LM, Gobom J, Jansen I, Dicks E, van der Lee SJ, et al.; ADNI; Smit AB, Blennow K, Scheltens P, Teunissen CE, Bertram L, Zetterberg H, et al. Cerebrospinal fluid tau levels are associated with abnormal neuronal plasticity markers in Alzheimer’s disease. Mol Neurodegener. 2022;17:27. [DOI] [PubMed] [PMC]

102.

Rawat P, Sehar U, Bisht J, Selman A, Culberson J, Reddy PH. Phosphorylated Tau in Alzheimer’s Disease and Other Tauopathies. Int J Mol Sci. 2022;23:12841. [DOI] [PubMed] [PMC]

103.

Villemagne VL, Ong K, Mulligan RS, Holl G, Pejoska S, Jones G, et al. Amyloid imaging with (18)F-florbetaben in Alzheimer disease and other dementias. J Nucl Med. 2011;52:1210–7. [DOI] [PubMed]

104.

Matsuda H, Okita K, Motoi Y, Mizuno T, Ikeda M, Sanjo N, et al. Clinical impact of amyloid PET using ¹⁸F-florbetapir in patients with cognitive impairment and suspected Alzheimer’s disease: a multicenter study. Ann Nucl Med. 2022;36:1039–49. [DOI] [PubMed] [PMC]

105.

Catafau AM, Bullich S. Amyloid PET imaging: applications beyond Alzheimer’s disease. Clin Transl Imaging. 2015;3:39–55. [DOI] [PubMed] [PMC]

106.

Varesi A, Carrara A, Pires VG, Floris V, Pierella E, Savioli G, et al. Blood-Based Biomarkers for Alzheimer’s Disease Diagnosis and Progression: An Overview. Cells. 2022;11:1367. [DOI] [PubMed] [PMC]

107.

Turner RS, Stubbs T, Davies DA, Albensi BC. Potential New Approaches for Diagnosis of Alzheimer’s Disease and Related Dementias. Front Neurol. 2020;11:496. [DOI] [PubMed] [PMC]

108.

Gao F. Integrated Positron Emission Tomography/Magnetic Resonance Imaging in clinical diagnosis of Alzheimer’s disease. Eur J Radiol. 2021;145:110017. [DOI] [PubMed]

109.

Zhou R, Ji B, Kong Y, Qin L, Ren W, Guan Y, et al. PET Imaging of Neuroinflammation in Alzheimer’s Disease. Front Immunol. 2021;12:739130. [DOI] [PubMed] [PMC]

110.

Gobbi LC, Knust H, Körner M, Honer M, Czech C, Belli S, et al. Identification of Three Novel Radiotracers for Imaging Aggregated Tau in Alzheimer’s Disease with Positron Emission Tomography. J Med Chem. 2017;60:7350–70. [DOI] [PubMed]

111.

Therriault J, Pascoal TA, Lussier FZ, Tissot C, Chamoun M, Bezgin G, et al. Biomarker modeling of Alzheimer’s disease using PET-based Braak staging. Nat Aging. 2022;2:526–35. [DOI] [PubMed] [PMC]

112.

George N, Gean E, Nandi A, Brašić JR, Wong DF. Chapter Sixteen - radiotracers used to image the brains of patients with alzheimer’s disease. In: Seeman P, Madras B, editors. Imaging of the human brain in health and disease. Boston: Academic Press; 2014. pp. 407–16. [DOI]

113.

Wang J, Jin C, Zhou J, Zhou R, Tian M, Lee HJ, et al. PET molecular imaging for pathophysiological visualization in Alzheimer’s disease. Eur J Nucl Med Mol Imaging. 2023;50:765–83. [DOI] [PubMed] [PMC]

114.

Nordberg A. Molecular imaging in Alzheimer’s disease: new perspectives on biomarkers for early diagnosis and drug development. Alzheimers Res Ther. 2011;3:34. [DOI] [PubMed] [PMC]

115.

Lauri C, Varani M, Bentivoglio V, Capriotti G, Signore A. Present status and future trends in molecular imaging of lymphocytes. Semin Nucl Med. 2023;53:125–34. [DOI] [PubMed] [PMC]

116.

Kim SJ, Ham H, Park YH, Choe YS, Kim YJ, Jang H, et al. Development and clinical validation of CT-based regional modified Centiloid method for amyloid PET. Alzheimers Res Ther. 2022;14:157. [DOI] [PubMed] [PMC]

117.

Patel S, Schmidt K, Hesterman J, Hoppin J. Advancing Drug Discovery and Development Using Molecular Imaging (ADDMI): an Interest Group of the World Molecular Imaging Society and an Inaugural Session on Positron Emission Tomography (PET). Mol Imaging Biol. 2017;19:348–56. [DOI] [PubMed]

118.

John K, Antigoni V. Imaging biomarkers of Alzheimer’s disease: The crucial role of molecular imaging. J Nucl Med. 2021;62:2019.

119.

Okamura N, Harada R, Ishiki A, Kikuchi A, Nakamura T, Kudo Y. The development and validation of tau PET tracers: current status and future directions. Clin Transl Imaging. 2018;6:305–16. [DOI] [PubMed] [PMC]

120.

Cistaro A, Alongi P, Caobelli F, Cassalia L. Radiotracers for Amyloid Imaging in Neurodegenerative Disease: State-of-the-Art and Novel Concepts. Curr Med Chem. 2018;25:3131–40. [DOI] [PubMed]

121.

Chun KA. Beta-amyloid imaging in dementia. Yeungnam Univ J Med. 2018;35:1–6. [DOI] [PubMed] [PMC]

122.

Salih S, Elliyanti A, Alkatheeri A, AlYafei F, Almarri B, Khan H. The Role of Molecular Imaging in Personalized Medicine. J Pers Med. 2023;13:369. [DOI] [PubMed] [PMC]

123.

Pemberton HG, Collij LE, Heeman F, Bollack A, Shekari M, Salvadó G, et al.; AMYPAD consortium. Quantification of amyloid PET for future clinical use: a state-of-the-art review. Eur J Nucl Med Mol Imaging. 2022;49:3508–28. [DOI] [PubMed] [PMC]

124.

Reiman EM, Chen K, Alexander GE, Caselli RJ, Bandy D, Osborne D, et al. Functional brain abnormalities in young adults at genetic risk for late-onset Alzheimer’s dementia. Proc Natl Acad Sci U S A. 2004;101:284–9. [DOI] [PubMed] [PMC]

125.

Klunk WE, Engler H, Nordberg A, Wang Y, Blomqvist G, Holt DP, et al. Imaging brain amyloid in Alzheimer’s disease with pittsburgh compound-B. Ann Neurol. 2004;55:306–19. [DOI] [PubMed] [PMC]

126.

Rowe CC, Ng S, Ackermann U, Gong SJ, Pike K, Savage G, et al. Imaging beta-amyloid burden in aging and dementia. Neurology. 2007;68:1718–25. [DOI] [PubMed]

127.

James OG, Doraiswamy PM, Borges-Neto S. PET Imaging of Tau Pathology in Alzheimer’s Disease and Tauopathies. Front Neurol. 2015;6:38. [DOI] [PubMed] [PMC]

128.

Wong DF, Rosenberg PB, Zhou Y, Kumar A, Raymont V, Ravert HT, et al. In vivo imaging of amyloid deposition in Alzheimer disease using the radioligand ¹⁸F-AV-45 (Flobetapir F 18). J Nucl Med. 2010;51:913–20. [DOI]

129.

Utianski RL, Whitwell JL, Schwarz CG, Senjem ML, Tosakulwong N, Duffy JR, et al. Tau-PET imaging with [18F]AV-1451 in primary progressive apraxia of speech. Cortex. 2018;99:358–74. [DOI]

130.

Harada R, Okamura N, Furumoto S, Furukawa K, Ishiki A, Tomita N, et al. 18F-THK5351: A Novel PET Radiotracer for Imaging Neurofibrillary Pathology in Alzheimer Disease. J Nucl Med. 2016;57:208–14. [DOI] [PubMed]

131.

Sabri O, Sabbagh MN, Seibyl J, Barthel H, Akatsu H, Ouchi Y, et al.; Florbetaben Phase 3 Study Group. Florbetaben PET imaging to detect amyloid beta plaques in Alzheimer’s disease: phase 3 study. Alzheimers Dement. 2015;11:964–74. [DOI] [PubMed]

132.

Yeo JM, Waddell B, Khan Z, Pal S. A systematic review and meta-analysis of ¹⁸F-labeled amyloid imaging in Alzheimer’s disease. Alzheimers Dement (am st). 2015;1:5–13. [DOI]

133.

Duff K, Horn KP, Hoffman JM. Long-term Changes in ¹⁸F-flutemetamol uptake in nondemented older adults. Alzheimer Dis Assoc Disord. 2019;33:113–7. [DOI]

134.

Wood H. [¹¹C]PBB3—a new PET ligand that identifies tau pathology in the brains of patients with AD. Nat Rev Neurol. 2013;9:599. [DOI]

135.

Swan A, Waddell B, Holloway G, Bak T, Colville S, Khan Z, et al. The diagnostic utility of 99mTc-HMPAO SPECT imaging: a retrospective case series from a tertiary referral early-onset cognitive disorders clinic. Dement Geriatr Cogn Disord. 2015;39:186–93. [DOI] [PubMed]

136.

Minoshima S, Giordani B, Berent S, Frey KA, Foster NL, Kuhl DE. Metabolic reduction in the posterior cingulate cortex in very early Alzheimer’s disease. Ann Neurol. 1997;42:85–94. [DOI] [PubMed]

137.

Silverman DH, Small GW, Chang CY, Lu CS, Kung De Aburto MA, Chen W, et al. Positron emission tomography in evaluation of dementia: Regional brain metabolism and long-term outcome. JAMA. 2001;286:2120–7. [DOI] [PubMed]

138.

Guedj E, Varrone A, Boellaard R, Albert NL, Barthel H, van Berckel B, et al. EANM procedure guidelines for brain PET imaging using [¹⁸F]FDG, version 3. Eur J Nucl Med Mol Imaging. 2022;49:632–51. [DOI] [PubMed] [PMC]

139.

Ohnishi T, Hoshi H, Nagamachi S, Jinnouchi S, Futami S, Watanabe K, et al. Regional cerebral blood flow study with 123I-IMP in patients with degenerative dementia. AJNR Am J Neuroradiol. 1991;12:513–20. [PubMed] [PMC]

140.

Hellman RS, Tikofsky RS, Collier BD, Hoffmann RG, Palmer DW, Glatt SL, et al. Alzheimer disease: quantitative analysis of I-123-iodoamphetamine SPECT brain imaging. Radiology. 1989;172:183–8. [DOI] [PubMed]

141.

Masterman DL, Mendez MF, Fairbanks LA, Cummings JL. Sensitivity, specificity, and positive predictive value of technetium 99-HMPAO SPECT in discriminating Alzheimer’s disease from other dementias. J Geriatr Psychiatry Neurol. 1997;10:15–21. [DOI] [PubMed]

142.

Holman BL, Devous MD Sr. Functional brain SPECT: the emergence of a powerful clinical method. J Nucl Med. 1992;33:1888–904. [PubMed]

143.

Imokawa T, Yokoyama K, Takahashi K, Oyama J, Tsuchiya J, Sanjo N, et al. Brain perfusion SPECT in dementia: what radiologists should know. Jpn J Radiol. 2024;42:1215–30. [DOI] [PubMed] [PMC]

144.

Borroni B, Anchisi D, Paghera B, Vicini B, Kerrouche N, Garibotto V, et al. Combined 99mTc-ECD SPECT and neuropsychological studies in MCI for the assessment of conversion to AD. Neurobiol Aging. 2006;27:24–31. [DOI] [PubMed]

145.

Watanabe H. Development of SPECT Probes for In Vivo Imaging of β-Amyloid and Tau Aggregates in the Alzheimer’s Disease Brain. Yakugaku Zasshi. 2017;137:1361–5. Japanese. [DOI] [PubMed]

146.

Talbot PR, Lloyd JJ, Snowden JS, Neary D, Testa HJ. A clinical role for 99mTc-HMPAO SPECT in the investigation of dementia? J Neurol Neurosurg Psychiatry. 1998;64:306–13. [DOI] [PubMed] [PMC]

147.

Bao W, Xie F, Zuo C, Guan Y, Huang YH. PET Neuroimaging of Alzheimer’s Disease: Radiotracers and Their Utility in Clinical Research. Front Aging Neurosci. 2021;13:624330. [DOI] [PubMed] [PMC]

148.

Landau SM, Thomas BA, Thurfjell L, Schmidt M, Margolin R, Mintun M, et al.; Alzheimer’s Disease Neuroimaging Initiative. Amyloid PET imaging in Alzheimer’s disease: a comparison of three radiotracers. Eur J Nucl Med Mol Imaging. 2014;41:1398–407. [DOI] [PubMed] [PMC]

149.

Ong KT, Villemagne VL, Bahar-Fuchs A, Lamb F, Langdon N, Catafau AM, et al. Aβ imaging with 18F-florbetaben in prodromal Alzheimer’s disease: a prospective outcome study. J Neurol Neurosurg Psychiatry. 2015;86:431–6. [DOI] [PubMed]

150.

Martínez G, Vernooij RW, Fuentes Padilla P, Zamora J, Flicker L, Bonfill Cosp X. 18F PET with florbetaben for the early diagnosis of Alzheimer’s disease dementia and other dementias in people with mild cognitive impairment (MCI). Cochrane Database Syst Rev. 2017;11:CD012216. [DOI] [PubMed] [PMC]

151.

Cummings J, Feldman HH, Scheltens P. The “rights” of precision drug development for Alzheimer’s disease. Alzheimers Res Ther. 2019;11:76. [DOI] [PubMed] [PMC]

152.

Son H, Jang K, Lee H, Kim SE, Kang KW, Lee H. Use of Molecular Imaging in Clinical Drug Development: a Systematic Review. Nucl Med Mol Imaging. 2019;53:208–15. [DOI] [PubMed] [PMC]

153.

Chen ZY, Wang YX, Lin Y, Zhang JS, Yang F, Zhou QL, et al. Advance of molecular imaging technology and targeted imaging agent in imaging and therapy. Biomed Res Int. 2014;2014:819324. [DOI] [PubMed] [PMC]

154.

Villemagne VL, Barkhof F, Garibotto V, Landau SM, Nordberg A, van Berckel BNM. Molecular Imaging Approaches in Dementia. Radiology. 2021;298:517–30. [DOI] [PubMed] [PMC]

155.

Teipel S, Gustafson D, Ossenkoppele R, Hansson O, Babiloni C, Wagner M, et al. Alzheimer disease: standard of diagnosis, treatment, care, and prevention. J Nucl Med. 2022;63:981–5. [DOI]

156.

Mathis CA, Mason NS, Lopresti BJ, Klunk WE. Development of positron emission tomography β-amyloid plaque imaging agents. Semin Nucl Med. 2012;42:423–32. [DOI] [PubMed] [PMC]

157.

Landau SM, Breault C, Joshi AD, Pontecorvo M, Mathis CA, Jagust WJ, et al.; Alzheimer’s Disease Neuroimaging Initiative. Amyloid-β imaging with Pittsburgh compound B and florbetapir: comparing radiotracers and quantification methods. J Nucl Med. 2013;54:70–7. [DOI] [PubMed] [PMC]

158.

Rowe CC, Pejoska S, Mulligan RS, Jones G, Chan JG, Svensson S, et al. Head-to-head comparison of ¹¹C-PiB and ¹⁸F-AZD4694 (NAV4694) for β-amyloid imaging in aging and dementia. J Nucl Med. 2013;54:880–6. [DOI]

159.

Clark CM, Schneider JA, Bedell BJ, Beach TG, Bilker WB, Mintun MA, et al.; AV45-A07 Study Group. Use of florbetapir-PET for imaging beta-amyloid pathology. JAMA. 2011;305:275–83. [DOI] [PubMed] [PMC]

160.

Shidahara M, Tashiro M, Okamura N, Furumoto S, Furukawa K, Watanuki S, et al. Evaluation of the biodistribution and radiation dosimetry of the ¹⁸F-labelled amyloid imaging probe [¹⁸F]FACT in humans. EJNMMI Res. 2013;3:32. [DOI]

161.

Scheinin NM, Tolvanen TK, Wilson IA, Arponen EM, Någren KA, Rinne JO. Biodistribution and radiation dosimetry of the amyloid imaging agent 11C-PIB in humans. J Nucl Med. 2007;48:128–33. [PubMed]

162.

Fan LY, Tzen KY, Chen YF, Chen TF, Lai YM, Yen RF, et al. The Relation Between Brain Amyloid Deposition, Cortical Atrophy, and Plasma Biomarkers in Amnesic Mild Cognitive Impairment and Alzheimer’s Disease. Front Aging Neurosci. 2018;10:175. [DOI] [PubMed] [PMC]

163.

Valotassiou V, Malamitsi J, Papatriantafyllou J, Dardiotis E, Tsougos I, Psimadas D, et al. SPECT and PET imaging in Alzheimer's disease. Ann Nucl Med. 2018;32:583–93. [DOI] [PubMed]

164.

Mattay VS, Fotenos AF, Ganley CJ, Marzella L. Brain Tau Imaging: Food and Drug Administration Approval of ¹⁸F-flortaucipir injection. J Nucl Med. 2020;61:1411–2. [DOI]

165.

Villemagne VL, Burnham S, Bourgeat P, Brown B, Ellis KA, Salvado O, et al.; Australian Imaging Biomarkers and Lifestyle (AIBL) Research Group. Amyloid β deposition, neurodegeneration, and cognitive decline in sporadic Alzheimer's disease: a prospective cohort study. Lancet Neurol. 2013;12:357–67. [DOI] [PubMed]

166.

Sinsky J, Pichlerova K, Hanes J. Tau Protein Interaction Partners and Their Roles in Alzheimer’s Disease and Other Tauopathies. Int J Mol Sci. 2021;22:9207. [DOI] [PubMed] [PMC]

167.

Yamin G, Teplow DB. Pittsburgh Compound-B (PiB) binds amyloid β-protein protofibrils. J Neurochem. 2017;140:210–5. [DOI] [PubMed] [PMC]

168.

Okamura N, Harada R, Furukawa K, Furumoto S, Tago T, Yanai K, et al. Advances in the development of tau PET radiotracers and their clinical applications. Ageing Res Rev. 2016;30:107–13. [DOI] [PubMed]

169.

Villemagne VL, Fodero-Tavoletti MT, Masters CL, Rowe CC. Tau imaging: early progress and future directions. Lancet Neurol. 2015;14:114–24. [DOI] [PubMed]

170.

Schöll M, Lockhart SN, Schonhaut DR, O’Neil JP, Janabi M, Ossenkoppele R, et al. PET Imaging of Tau Deposition in the Aging Human Brain. Neuron. 2016;89:971–82. [DOI] [PubMed] [PMC]

171.

Lois C, Gonzalez I, Johnson KA, Price JC. PET imaging of tau protein targets: a methodology perspective. Brain Imaging Behav. 2019;13:333–44. [DOI] [PubMed] [PMC]

172.

Beyer L, Brendel M. Imaging of Tau Pathology in Neurodegenerative Diseases: An Update. Semin Nucl Med. 2021;51:253–63. [DOI] [PubMed]

173.

Thientunyakit T, Shiratori S, Ishii K, Gelovani JG. Molecular PET imaging in Alzheimer’s disease. J Med Biol Eng. 2022;42:301–17. [DOI]

174.

Werry EL, Bright FM, Piguet O, Ittner LM, Halliday GM, Hodges JR, et al. Recent Developments in TSPO PET Imaging as A Biomarker of Neuroinflammation in Neurodegenerative Disorders. Int J Mol Sci. 2019;20:3161. [DOI] [PubMed] [PMC]

175.

Huang J. Novel brain PET imaging agents: Strategies for imaging neuroinflammation in Alzheimer’s disease and mild cognitive impairment. Front Immunol. 2022;13:1010946. [DOI] [PubMed] [PMC]

176.

Tiwari S, Atluri V, Kaushik A, Yndart A, Nair M. Alzheimer’s disease: pathogenesis, diagnostics, and therapeutics. Int J Nanomedicine. 2019;14:5541–54. [DOI] [PubMed] [PMC]

177.

Leocadi M, Canu E, Calderaro D, Corbetta D, Filippi M, Agosta F. An update on magnetic resonance imaging markers in AD. Ther Adv Neurol Disord. 2020;13:1756286420947986. [DOI] [PubMed] [PMC]

178.

Villa C, Lavitrano M, Salvatore E, Combi R. Molecular and Imaging Biomarkers in Alzheimer's Disease: A Focus on Recent Insights. J Pers Med. 2020;10:61. [DOI] [PubMed] [PMC]

179.

Albert MS, DeKosky ST, Dickson D, Dubois B, Feldman HH, Fox NC, et al. The diagnosis of mild cognitive impairment due to Alzheimer’s disease: recommendations from the National Institute on Aging-Alzheimer’s Association workgroups on diagnostic guidelines for Alzheimer’s disease. Alzheimers Dement. 2011;7:270–9. [DOI] [PubMed] [PMC]

180.

Knopman DS, Parisi JE, Salviati A, Floriach-Robert M, Boeve BF, Ivnik RJ, et al. Neuropathology of cognitively normal elderly. J Neuropathol Exp Neurol. 2003;62:1087–95. [DOI] [PubMed]

181.

Salloway S, Sperling R, Fox NC, Blennow K, Klunk W, Raskind M, et al.; Bapineuzumab 301 and 302 Clinical Trial Investigators. Two phase 3 trials of bapineuzumab in mild-to-moderate Alzheimer’s disease. N Engl J Med. 2014;370:322–33. [DOI] [PubMed] [PMC]

182.

van Oostveen WM, de Lange ECM. Imaging Techniques in Alzheimer’s Disease: A Review of Applications in Early Diagnosis and Longitudinal Monitoring. Int J Mol Sci. 2021;22:2110. [DOI] [PubMed] [PMC]

183.

J Koutsikos, A Velidaki. Imaging Biomarkers of Alzheimer’s disease: The crucial role of Molecular Imaging. J Nucl Med. 2021;62.

184.

Vandenberghe R, Van Laere K, Ivanoiu A, Salmon E, Bastin C, Triau E, et al. 18F-flutemetamol amyloid imaging in Alzheimer disease and mild cognitive impairment: a phase 2 trial. Ann Neurol. 2010;68:319–29. [DOI] [PubMed]

185.

Ossenkoppele R, Lyoo CH, Sudre CH, van Westen D, Cho H, Ryu YH, et al. Distinct tau PET patterns in atrophy-defined subtypes of Alzheimer’s disease. Alzheimers Dement. 2020;16:335–44. [DOI] [PubMed] [PMC]

186.

Klunk WE, Koeppe RA, Price JC, Benzinger TL, Devous MD Sr, Jagust WJ, et al. The Centiloid Project: standardizing quantitative amyloid plaque estimation by PET. Alzheimers Dement. 2015;11:1–15.e4. [DOI] [PubMed] [PMC]

187.

Agarwal R, Brunelli SM, Williams K, Mitchell MD, Feldman HI, Umscheid CA. Gadolinium-based contrast agents and nephrogenic systemic fibrosis: a systematic review and meta-analysis. Nephrol Dial Transplant. 2009;24:856–63. [DOI] [PubMed]

188.

Marquié M, Normandin MD, Vanderburg CR, Costantino IM, Bien EA, Rycyna LG, et al. Validating novel tau positron emission tomography tracer [F-18]-AV-1451 (T807) on postmortem brain tissue. Ann Neurol. 2015;78:787–800. [DOI]

189.

Chien DT, Bahri S, Szardenings AK, Walsh JC, Mu F, Su MY, et al. Early Clinical PET Imaging Results with the Novel PHF-Tau Radioligand [F-18]-T807. J Alzheimer’s Dis. 2013;34:457–68. [DOI]

190.

Booij J, Knol RJ. SPECT imaging of the dopaminergic system in (premotor) Parkinson’s disease. Parkinsonism Relat Disord. 2007;13:S425–8. [DOI] [PubMed]

191.

Seibyl JP, Marek KL, Quinlan D, Sheff K, Zoghbi S, Zea-Ponce Y, et al. Decreased single-photon emission computed tomographic [123I]beta-CIT striatal uptake correlates with symptom severity in Parkinson’s disease. Ann Neurol. 1995;38:589–98. [DOI] [PubMed]

192.

Perani D, Cerami C, Caminiti SP, Santangelo R, Coppi E, Ferrari L, et al. Cross-validation of biomarkers for the early differential diagnosis and prognosis of dementia in a clinical setting. Eur J Nucl Med Mol Imaging. 2016;43:499–508. [DOI] [PubMed]

193.

Barthel H, Sabri O. Clinical Use and Utility of Amyloid Imaging. J Nucl Med. 2017;58:1711–7. [DOI] [PubMed]

194.

Gulani V, Calamante F, Shellock FG, Kanal E, Reeder SB; International Society for Magnetic Resonance in Medicine. Gadolinium deposition in the brain: summary of evidence and recommendations. Lancet Neurol. 2017;16:564–70. [DOI] [PubMed]

195.

McDonald RJ, McDonald JS, Kallmes DF, Jentoft ME, Murray DL, Thielen KR, et al. Intracranial Gadolinium Deposition after Contrast-enhanced MR Imaging. Radiology. 2015;275:772–82. [DOI] [PubMed]

196.

Mattsson N, Palmqvist S, Stomrud E, Vogel J, Hansson O. Staging β-Amyloid Pathology With Amyloid Positron Emission Tomography. JAMA Neurol. 2019;76:1319–29. [DOI] [PubMed] [PMC]

197.

Leuzy A, Smith R, Ossenkoppele R, Santillo A, Borroni E, Klein G, et al. Diagnostic Performance of RO948 F 18 Tau Positron Emission Tomography in the Differentiation of Alzheimer Disease From Other Neurodegenerative Disorders. JAMA Neurol. 2020;77:955–65. [DOI] [PubMed] [PMC]

198.

Martínez-Torteya A, Treviño V, Tamez-Peña JG. Improved Diagnostic Multimodal Biomarkers for Alzheimer’s Disease and Mild Cognitive Impairment. Biomed Res Int. 2015;2015:961314. [DOI] [PubMed] [PMC]

199.

Hansson O. Biomarkers for neurodegenerative diseases. Nat Med. 2021;27:954–63. [DOI] [PubMed]

200.

Petersen RC, Aisen P, Boeve BF, Geda YE, Ivnik RJ, Knopman DS, et al. Mild cognitive impairment due to Alzheimer disease in the community. Ann Neurol. 2013;74:199–208. [DOI] [PubMed] [PMC]

201.

Dubois B, Villain N, Frisoni GB, Rabinovici GD, Sabbagh M, Cappa S, et al. Clinical diagnosis of Alzheimer’s disease: recommendations of the International Working Group. Lancet Neurol. 2021;20:484–96. [DOI] [PubMed] [PMC]

202.

Livingston G, Huntley J, Sommerlad A, Ames D, Ballard C, Banerjee S, et al. Dementia prevention, intervention, and care: 2020 report of the Lancet Commission. Lancet. 2020;396:413–46. [DOI] [PubMed] [PMC]

203.

Sperling RA, Aisen PS, Beckett LA, Bennett DA, Craft S, Fagan AM, et al. Toward defining the preclinical stages of Alzheimer’s disease: recommendations from the National Institute on Aging-Alzheimer’s Association workgroups on diagnostic guidelines for Alzheimer’s disease. Alzheimers Dement. 2011;7:280–92. [DOI] [PubMed] [PMC]

204.

McKhann GM, Knopman DS, Chertkow H, Hyman BT, Jack CR Jr, Kawas CH, et al. The diagnosis of dementia due to Alzheimer’s disease: recommendations from the National Institute on Aging-Alzheimer’s Association workgroups on diagnostic guidelines for Alzheimer’s disease. Alzheimers Dement. 2011;7:263–9. [DOI] [PubMed] [PMC]

205.

Karlawish J. Addressing the ethical, policy, and social challenges of preclinical Alzheimer disease. Neurology. 2011;77:1487–93. [DOI] [PubMed] [PMC]

206.

Chiong W, Tsou AY, Simmons Z, Bonnie RJ, Russell JA; Ethics, Law, and Humanities Committee (a joint committee of the American Academy of Neurology, American Neurological Association, and Child Neurology Society). Ethical Considerations in Dementia Diagnosis and Care: AAN Position Statement. Neurology. 2021;97:80–9. [DOI] [PubMed]

207.

Jack CR Jr, Knopman DS, Jagust WJ, Petersen RC, Weiner MW, Aisen PS, et al. Tracking pathophysiological processes in Alzheimer’s disease: an updated hypothetical model of dynamic biomarkers. Lancet Neurol. 2013;12:207–16. [DOI] [PubMed] [PMC]

208.

Jack CR Jr, Petersen RC, Xu Y, O’Brien PC, Smith GE, Ivnik RJ, et al. Rates of hippocampal atrophy correlate with change in clinical status in aging and AD. Neurology. 2000;55:484–89. [DOI] [PubMed] [PMC]

209.

Ávila-Villanueva M, Marcos Dolado A, Gómez-Ramírez J, Fernández-Blázquez M. Brain Structural and Functional Changes in Cognitive Impairment Due to Alzheimer’s Disease. Front Psychol. 2022;13:886619. [DOI] [PubMed] [PMC]

210.

Rowe CC, Ellis KA, Rimajova M, Bourgeat P, Pike KE, Jones G, et al. Amyloid imaging results from the Australian Imaging, Biomarkers and Lifestyle (AIBL) study of aging. Neurobiol Aging. 2010;31:1275–83. [DOI] [PubMed]

211.

Aderinto N, Olatunji D, Abdulbasit M, Edun M. The essential role of neuroimaging in diagnosing and managing cerebrovascular disease in Africa: a review. Ann Med. 2023;55:2251490. [DOI] [PubMed] [PMC]

212.

Lindner JR, Link J. Molecular Imaging in Drug Discovery and Development. Circ Cardiovasc Imaging. 2018;11:e005355. [DOI] [PubMed] [PMC]

213.

Luo X, Tan B, Zhao X, Zhang Z, Wang G, Wang T, et al. Harnessing the power of molecular imaging for drug discovery and development. iRADIOLOGY. 2023;1:362–77. [DOI]

214.

Qiao Y, Chi Y, Zhang Q, Ma Y. Safety and efficacy of lecanemab for Alzheimer's disease: a systematic review and meta-analysis of randomized clinical trials. Front Aging Neurosci. 2023;15:1169499. [DOI] [PubMed] [PMC]

215.

Budd Haeberlein S, Aisen PS, Barkhof F, Chalkias S, Chen T, Cohen S, et al. Two Randomized Phase 3 Studies of Aducanumab in Early Alzheimer’s Disease. J Prev Alzheimers Dis. 2022;9:197–210. [DOI] [PubMed]

216.

van Dyck CH, Swanson CJ, Aisen P, Bateman RJ, Chen C, Gee M, et al. Lecanemab in Early Alzheimer’s Disease. N Engl J Med. 2023;388:9–21. [DOI] [PubMed]

217.

Wu W, Ji Y, Wang Z, Wu X, Li J, Gu F, et al. The FDA-approved anti-amyloid-β monoclonal antibodies for the treatment of Alzheimer’s disease: a systematic review and meta-analysis of randomized controlled trials. Eur J Med Res. 2023;28:544. [DOI] [PubMed] [PMC]

218.

Volloch V, Rits-Volloch S. Effect of Lecanemab in Early Alzheimer’s Disease: Mechanistic Interpretation in the Amyloid Cascade Hypothesis 2.0 Perspective. J Alzheimers Dis. 2023;93:1277–84. [DOI] [PubMed] [PMC]

219.

Sevigny J, Chiao P, Bussière T, Weinreb PH, Williams L, Maier M, et al. The antibody aducanumab reduces Aβ plaques in Alzheimer’s disease. Nature. 2016;537:50–6. [DOI] [PubMed]

220.

Yadollahikhales G, Rojas JC. Anti-Amyloid Immunotherapies for Alzheimer’s Disease: A 2023 Clinical Update. Neurotherapeutics. 2023;20:914–31. [DOI] [PubMed] [PMC]

221.

Huang LK, Kuan YC, Lin HW, Hu CJ. Clinical trials of new drugs for Alzheimer disease: a 2020-2023 update. J Biomed Sci. 2023;30:83. [DOI] [PubMed] [PMC]