REFERENCES
1. 2019 Dementia Forecasting Collaborators. Estimation of the global prevalence of dementia in 2019 and forecasted prevalence in 2050: an analysis for the Global Burden of Disease Study 2019. Lancet Public Health. 2022;7:e105-25.
2. Mukadam N, Wolters FJ, Walsh S, et al. Changes in prevalence and incidence of dementia and risk factors for dementia: an analysis from cohort studies. Lancet Public Health. 2024;9:e443-60.
3. Koriath CAM, Kenny J, Ryan NS, et al. Genetic testing in dementia - utility and clinical strategies. Nat Rev Neurol. 2021;17:23-36.
4. Seath P, Macedo-Orrego LE, Velayudhan L. Clinical characteristics of early-onset versus late-onset Alzheimer’s disease: a systematic review and meta-analysis. Int Psychogeriatr. 2024;36:1093-109.
5. Sims R, Hill M, Williams J. The multiplex model of the genetics of Alzheimer’s disease. Nat Neurosci. 2020;23:311-22.
6. Xiao X, Liu H, Liu X, Zhang W, Zhang S, Jiao B.
7. Nudelman KNH, Jackson T, Rumbaugh M, et al; DIAN/DIAN-TU Clinical/Genetics Committee. Pathogenic variants in the Longitudinal Early-onset Alzheimer’s Disease Study cohort. Alzheimers Dement. 2023;19 Suppl 9:S64-73.
8. Jiao B, Liu H, Guo L, et al. The role of genetics in neurodegenerative dementia: a large cohort study in South China. NPJ Genom Med. 2021;6:69.
9. Serrano-Pozo A, Das S, Hyman BT. APOE and Alzheimer’s disease: advances in genetics, pathophysiology, and therapeutic approaches. Lancet Neurol. 2021;20:68-80.
10. Belloy ME, Andrews SJ, Le Guen Y, et al. APOE genotype and Alzheimer disease risk across age, sex, and population ancestry. JAMA Neurol. 2023;80:1284-94.
11. Fortea J, Pegueroles J, Alcolea D, et al. APOE4 homozygozity represents a distinct genetic form of Alzheimer’s disease. Nat Med. 2024;30:1284-91.
12. Chemparathy A, Le Guen Y, Chen S, et al. APOE loss-of-function variants: compatible with longevity and associated with resistance to Alzheimer’s disease pathology. Neuron. 2024;112:1110-1116.e5.
13. Harold D, Abraham R, Hollingworth P, et al. Genome-wide association study identifies variants at CLU and PICALM associated with Alzheimer’s disease. Nat Genet. 2009;41:1088-93.
14. Lambert JC, Heath S, Even G, et al; European Alzheimer’s Disease Initiative Investigators. Genome-wide association study identifies variants at CLU and CR1 associated with Alzheimer’s disease. Nat Genet. 2009;41:1094-9.
15. Hollingworth P, Harold D, Sims R, et al; Alzheimer’s Disease Neuroimaging Initiative. Common variants at ABCA7, MS4A6A/MS4A4E, EPHA1, CD33 and CD2AP are associated with Alzheimer’s disease. Nat Genet. 2011;43:429-35.
16. Naj AC, Jun G, Beecham GW, et al. Common variants at MS4A4/MS4A6E, CD2AP, CD33 and EPHA1 are associated with late-onset Alzheimer’s disease. Nat Genet. 2011;43:436-41.
17. Lambert JC, Ibrahim-Verbaas CA, Harold D, et al; European Alzheimer’s Disease Initiative (EADI). Meta-analysis of 74,046 individuals identifies 11 new susceptibility loci for Alzheimer’s disease. Nat Genet. 2013;45:1452-8.
18. Jansen IE, Savage JE, Watanabe K, et al. Genome-wide meta-analysis identifies new loci and functional pathways influencing Alzheimer’s disease risk. Nat Genet. 2019;51:404-13.
19. Kunkle BW, Grenier-Boley B, Sims R, et al; Alzheimer Disease Genetics Consortium (ADGC). Genetic meta-analysis of diagnosed Alzheimer’s disease identifies new risk loci and implicates Aβ, tau, immunity and lipid processing. Nat Genet. 2019;51:414-30.
20. Wightman DP, Jansen IE, Savage JE, et al; 23andMe Research Team. A genome-wide association study with 1,126,563 individuals identifies new risk loci for Alzheimer’s disease. Nat Genet. 2021;53:1276-82.
21. Bellenguez C, Küçükali F, Jansen IE, et al; EADB. New insights into the genetic etiology of Alzheimer’s disease and related dementias. Nat Genet. 2022;54:412-36.
22. Andrews SJ, Renton AE, Fulton-Howard B, Podlesny-Drabiniok A, Marcora E, Goate AM. The complex genetic architecture of Alzheimer’s disease: novel insights and future directions. EBioMedicine. 2023;90:104511.
23. Jiao B, Xiao X, Yuan Z, et al. Associations of risk genes with onset age and plasma biomarkers of Alzheimer’s disease: a large case-control study in mainland China. Neuropsychopharmacology. 2022;47:1121-7.
24. Zhou X, Chen Y, Mok KY, et al; Alzheimer’s Disease Neuroimaging Initiative. Identification of genetic risk factors in the Chinese population implicates a role of immune system in Alzheimer’s disease pathogenesis. Proc Natl Acad Sci U S A. 2018;115:1697-706.
25. Jia L, Li F, Wei C, et al. Prediction of Alzheimer’s disease using multi-variants from a Chinese genome-wide association study. Brain. 2021;144:924-37.
26. Ge YJ, Chen SD, Wu BS, et al. Genome-wide meta-analysis identifies ancestry-specific loci for Alzheimer’s disease. Alzheimers Dement. 2024;20:6243-56.
27. Guerreiro R, Wojtas A, Bras J, et al; Alzheimer Genetic Analysis Group.
28. Cruchaga C, Karch CM, Jin SC, et al; Alzheimer’s Research UK (ARUK) Consortium. Rare coding variants in the phospholipase D3 gene confer risk for Alzheimer’s disease. Nature. 2014;505:550-4.
29. Roeck A, Van Broeckhoven C, Sleegers K. The role of ABCA7 in Alzheimer’s disease: evidence from genomics, transcriptomics and methylomics. Acta Neuropathol. 2019;138:201-20.
30. Wetzel-Smith MK, Hunkapiller J, Bhangale TR, et al; Alzheimer’s Disease Genetics Consortium. A rare mutation in UNC5C predisposes to late-onset Alzheimer’s disease and increases neuronal cell death. Nat Med. 2014;20:1452-7.
31. Campion D, Charbonnier C, Nicolas G.
32. Sims R, van der Lee SJ, Naj AC, et al; ARUK Consortium. Rare coding variants in PLCG2, ABI3, and TREM2 implicate microglial-mediated innate immunity in Alzheimer’s disease. Nat Genet. 2017;49:1373-84.
33. Holstege H, Hulsman M, Charbonnier C, et al. Exome sequencing identifies rare damaging variants in ATP8B4 and ABCA1 as risk factors for Alzheimer’s disease. Nat Genet. 2022;54:1786-94.
34. Qin W, Zhou A, Zuo X, et al. Exome sequencing revealed PDE11A as a novel candidate gene for early-onset Alzheimer’s disease. Hum Mol Genet. 2021;30:811-22.
35. Zhang DF, Fan Y, Xu M, et al; Alzheimer’s Disease Neuroimaging Initiative (ADNI).
36. Luo R, Fan Y, Yang J, et al. A novel missense variant in ACAA1 contributes to early-onset Alzheimer’s disease, impairs lysosomal function, and facilitates amyloid-β pathology and cognitive decline. Signal Transduct Target Ther. 2021;6:325.
37. Liao X, Cai F, Sun Z, et al. Identification of Alzheimer’s disease-associated rare coding variants in the ECE2 gene. JCI Insight. 2020;5:135119.
38. Jiang Y, Wan M, Xiao X, et al. GSN gene frameshift mutations in Alzheimer’s disease. J Neurol Neurosurg Psychiatry. 2023;94:436-47.
39. Xiao X, Liu H, Yao R, et al.
40. Collins RL, Talkowski ME. Diversity and consequences of structural variation in the human genome. Nat Rev Genet. 2025;26:443-62.
41. Zarrei M, MacDonald JR, Merico D, Scherer SW. A copy number variation map of the human genome. Nat Rev Genet. 2015;16:172-83.
42. Cacace R, Sleegers K, Van Broeckhoven C. Molecular genetics of early-onset Alzheimer’s disease revisited. Alzheimers Dement. 2016;12:733-48.
43. Lee WP, Tucci AA, Conery M, et al. Copy number variation identification on 3,800 Alzheimer’s disease whole genome sequencing data from the Alzheimer’s disease sequencing project. Front Genet. 2021;12:752390.
44. Ming C, Wang M, Wang Q, et al. Whole genome sequencing-based copy number variations reveal novel pathways and targets in Alzheimer’s disease. Alzheimers Dement. 2022;18:1846-67.
46. Roeck A, Duchateau L, Van Dongen J, et al; BELNEU Consortium. An intronic VNTR affects splicing of ABCA7 and increases risk of Alzheimer’s disease. Acta Neuropathol. 2018;135:827-37.
47. Jiao B, Zhou L, Zhou Y, et al. Identification of expanded repeats in NOTCH2NLC in neurodegenerative dementias. Neurobiol Aging. 2020;89:142.e1-7.
48. Wu W, Yu J, Qian X, et al. Intermediate-length CGG repeat expansion in NOTCH2NLC is associated with pathologically confirmed Alzheimer’s disease. Neurobiol Aging. 2022;120:189-95.
49. Zhang X, Farrell JJ, Tong T, et al; Alzheimer’s Disease Sequencing Project. Association of mitochondrial variants and haplogroups identified by whole exome sequencing with Alzheimer’s disease. Alzheimers Dement. 2022;18:294-306.
50. Grossman M, Seeley WW, Boxer AL, et al. Frontotemporal lobar degeneration. Nat Rev Dis Primers. 2023;9:40.
51. Mol MO, van Rooij JGJ, Wong TH, et al. Underlying genetic variation in familial frontotemporal dementia: sequencing of 198 patients. Neurobiol Aging. 2021;97:148.e9-148.e16.
52. Leveille E, Ross OA, Gan-Or Z. Tau and MAPT genetics in tauopathies and synucleinopathies. Parkinsonism Relat Disord. 2021;90:142-54.
53. Amin S, Carling G, Gan L. New insights and therapeutic opportunities for progranulin-deficient frontotemporal dementia. Curr Opin Neurobiol. 2022;72:131-9.
54. Tang X, Toro A, T G S, et al. Divergence, convergence, and therapeutic implications: a cell biology perspective of C9ORF72-ALS/FTD. Mol Neurodegener. 2020;15:34.
55. Grover A, Houlden H, Baker M, 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.
56. Rademakers R, Cruts M, van Broeckhoven C. The role of tau (MAPT) in frontotemporal dementia and related tauopathies. Hum Mutat. 2004;24:277-95.
57. Woollacott IO, Mead S. The C9ORF72 expansion mutation: gene structure, phenotypic and diagnostic issues. Acta Neuropathol. 2014;127:319-32.
58. Majounie E, Renton AE, Mok K, et al; Chromosome 9-ALS/FTD Consortium. Frequency of the C9orf72 hexanucleotide repeat expansion in patients with amyotrophic lateral sclerosis and frontotemporal dementia: a cross-sectional study. Lancet Neurol. 2012;11:323-30.
59. Xu T, Weng L, Zhang C, et al. Genetic spectrum features and diagnostic accuracy of four plasma biomarkers in 248 Chinese patients with frontotemporal dementia. Alzheimers Dement. 2024;20:7281-95.
60. Huang M, Modeste E, Dammer E, et al. Network analysis of the progranulin-deficient mouse brain proteome reveals pathogenic mechanisms shared in human frontotemporal dementia caused by GRN mutations. Acta Neuropathol Commun. 2020;8:163.
61. Jiao B, Xiao T, Hou L, et al. High prevalence of CHCHD10 mutation in patients with frontotemporal dementia from China. Brain. 2016;139:e21.
62. Van Deerlin VM, Sleiman PM, Martinez-Lage M, et al. Common variants at 7p21 are associated with frontotemporal lobar degeneration with TDP-43 inclusions. Nat Genet. 2010;42:234-9.
63. Ferrari R, Hernandez DG, Nalls MA, et al. Frontotemporal dementia and its subtypes: a genome-wide association study. Lancet Neurol. 2014;13:686-99.
64. Pottier C, Ren Y, Perkerson RB 3rd, et al. Genome-wide analyses as part of the international FTLD-TDP whole-genome sequencing consortium reveals novel disease risk factors and increases support for immune dysfunction in FTLD. Acta Neuropathol. 2019;137:879-99.
65. Coppola G, Chinnathambi S, Lee JJ, et al; Alzheimer’s Disease Genetics Consortium. Evidence for a role of the rare p.A152T variant in MAPT in increasing the risk for FTD-spectrum and Alzheimer’s diseases. Hum Mol Genet. 2012;21:3500-12.
66. Reus LM, Jansen IE, Mol MO, et al. Genome-wide association study of frontotemporal dementia identifies a C9ORF72 haplotype with a median of 12-G4C2 repeats that predisposes to pathological repeat expansions. Transl Psychiatry. 2021;11:451.
67. Kaivola K, Chia R, Ding J, et al; American Genome Center. Genome-wide structural variant analysis identifies risk loci for non-Alzheimer’s dementias. Cell Genom. 2023;3:100316.
68. Jellinger KA, Korczyn AD. Are dementia with Lewy bodies and Parkinson’s disease dementia the same disease? BMC Med. 2018;16:34.
69. Palushaj B, Lewis SJG, Abdelnour C. What is the future for dementia with Lewy bodies? J Neurol. 2024;272:43.
70. Guerreiro R, Ross OA, Kun-Rodrigues C, et al. Investigating the genetic architecture of dementia with Lewy bodies: a two-stage genome-wide association study. Lancet Neurol. 2018;17:64-74.
71. Chia R, Sabir MS, Bandres-Ciga S, et al; American Genome Center. Genome sequencing analysis identifies new loci associated with Lewy body dementia and provides insights into its genetic architecture. Nat Genet. 2021;53:294-303.
72. Larsson V, Torisson G, Londos E. Relative survival in patients with dementia with Lewy bodies and Parkinson’s disease dementia. PLoS One. 2018;13:e0202044.
73. Guella I, Evans DM, Szu-Tu C, et al; SNCA Cognition Study Group. α-synuclein genetic variability: a biomarker for dementia in Parkinson disease. Ann Neurol. 2016;79:991-9.
74. Davis MY, Johnson CO, Leverenz JB, et al. Association of GBA mutations and the E326K polymorphism with motor and cognitive progression in Parkinson disease. JAMA Neurol. 2016;73:1217-24.
75. Winder-Rhodes SE, Hampshire A, Rowe JB, et al. Association between MAPT haplotype and memory function in patients with Parkinson’s disease and healthy aging individuals. Neurobiol Aging. 2015;36:1519-28.
76. Real R, Martinez-Carrasco A, Reynolds RH, et al. Association between the LRP1B and APOE loci and the development of Parkinson’s disease dementia. Brain. 2023;146:1873-87.
77. Tian Y, Zhou L, Gao J, et al. Clinical features of NOTCH2NLC-related neuronal intranuclear inclusion disease. J Neurol Neurosurg Psychiatry. 2022;93:1289-98.
78. Tai H, Wang A, Zhang Y, et al; China NIID Collaboration Alliance. Clinical features and classification of neuronal intranuclear inclusion disease. Neurol Genet. 2023;9:e200057.
79. Tian Y, Wang JL, Huang W, et al. Expansion of human-specific GGC repeat in neuronal intranuclear inclusion disease-related disorders. Am J Hum Genet. 2019;105:166-76.
80. Sone J, Mitsuhashi S, Fujita A, et al. Long-read sequencing identifies GGC repeat expansions in NOTCH2NLC associated with neuronal intranuclear inclusion disease. Nat Genet. 2019;51:1215-21.
81. Chen Z, Yan Yau W, Jaunmuktane Z, et al; Genomics England Research Consortium. Neuronal intranuclear inclusion disease is genetically heterogeneous. Ann Clin Transl Neurol. 2020;7:1716-25.
82. Huang XR, Tang BS, Jin P, Guo JF. The phenotypes and mechanisms of NOTCH2NLC-related GGC repeat expansion disorders: a comprehensive review. Mol Neurobiol. 2022;59:523-34.
83. Chen Z, Xu Z, Cheng Q, et al. Phenotypic bases of NOTCH2NLC GGC expansion positive neuronal intranuclear inclusion disease in a Southeast Asian cohort. Clin Genet. 2020;98:274-81.
84. Zeng T, Chen Y, Huang H, et al. Neuronal intranuclear inclusion disease with NOTCH2NLC GGC repeat expansion: a systematic review and challenges of phenotypic characterization. Aging Dis. 2024;16:578-97.
87. Ross CA, Aylward EH, Wild EJ, et al. Huntington disease: natural history, biomarkers and prospects for therapeutics. Nat Rev Neurol. 2014;10:204-16.
88. Krause A, Anderson DG, Ferreira-Correia A, et al. Huntington disease-like 2: insight into neurodegeneration from an African disease. Nat Rev Neurol. 2024;20:36-49.
90. Zerr I, Ladogana A, Mead S, Hermann P, Forloni G, Appleby BS. Creutzfeldt-Jakob disease and other prion diseases. Nat Rev Dis Primers. 2024;10:14.
91. Baiardi S, Rossi M, Capellari S, Parchi P. Recent advances in the histo-molecular pathology of human prion disease. Brain Pathol. 2019;29:278-300.
92. Uttley L, Carroll C, Wong R, Hilton DA, Stevenson M. Creutzfeldt-Jakob disease: a systematic review of global incidence, prevalence, infectivity, and incubation. Lancet Infect Dis. 2020;20:e2-e10.
93. Piñar-Morales R, Barrero-Hernández F, Aliaga-Martínez L. Human prion diseases: an overview. Med Clin. 2023;160:554-60.
94. Ladogana A, Puopolo M, Croes EA, et al. Mortality from Creutzfeldt-Jakob disease and related disorders in Europe, Australia, and Canada. Neurology. 2005;64:1586-91.
95. Mead S, Lloyd S, Collinge J. Genetic factors in mammalian prion diseases. Annu Rev Genet. 2019;53:117-47.
96. Kim MO, Takada LT, Wong K, Forner SA, Geschwind MD. Genetic PrP prion diseases. Cold Spring Harb Perspect Biol. 2018;10:a033134.
97. Lee HS, Sambuughin N, Cervenakova L, et al. Ancestral origins and worldwide distribution of the PRNP 200K mutation causing familial Creutzfeldt-Jakob disease. Am J Hum Genet. 1999;64:1063-70.
98. Brown P, Gálvez S, Goldfarb LG, et al. Familial Creutzfeldt-Jakob disease in Chile is associated with the codon 200 mutation of the PRNP amyloid precursor gene on chromosome 20. J Neurol Sci. 1992;112:65-7.
99. Mead S, Poulter M, Beck J, et al. Inherited prion disease with six octapeptide repeat insertional mutation--molecular analysis of phenotypic heterogeneity. Brain. 2006;129:2297-317.
100. McDonough GA, Cheng Y, Morillo K, et al. Neuropathologically-directed profiling of PRNP somatic and germline variants in sporadic human prion disease. bioRxiv. ;2024:2024.
101. Kim YC, Jeong BH. The first meta-analysis of the M129V single-nucleotide polymorphism (SNP) of the prion protein gene (PRNP) with sporadic Creutzfeldt-Jakob disease. Cells. 2021;10:3132.
102. Alperovitch A, Zerr I, Pocchiari M, et al. Codon 129 prion protein genotype and sporadic Creutzfeldt-Jakob disease. Lancet. 1999;353:1673-4.
103. Mead S, Uphill J, Beck J, et al. Genome-wide association study in multiple human prion diseases suggests genetic risk factors additional to PRNP. Hum Mol Genet. 2012;21:1897-906.
104. Sanchez-Juan P, Bishop MT, Kovacs GG, et al. A genome wide association study links glutamate receptor pathway to sporadic Creutzfeldt-Jakob disease risk. PLoS One. 2014;10:e0123654.
105. Jones E, Hummerich H, Viré E, et al. Identification of novel risk loci and causal insights for sporadic Creutzfeldt-Jakob disease: a genome-wide association study. Lancet Neurol. 2020;19:840-8.
106. Hummerich H, Speedy H, Campbell T, et al. Genome wide association study of clinical duration and age at onset of sporadic CJD. PLoS One. 2024;19:e0304528.
