Genomics and Functional Genomics of Alzheimer's Disease.
Alzheimer’s disease
Functional genomics
Genome-wide association studies
Genomics
SNPs
Journal
Neurotherapeutics : the journal of the American Society for Experimental NeuroTherapeutics
ISSN: 1878-7479
Titre abrégé: Neurotherapeutics
Pays: United States
ID NLM: 101290381
Informations de publication
Date de publication:
01 2022
01 2022
Historique:
accepted:
25
10
2021
pubmed:
23
12
2021
medline:
27
5
2022
entrez:
22
12
2021
Statut:
ppublish
Résumé
Alzheimer's disease (AD) is a complex and multifactorial neurodegenerative disease. Due to its long clinical course and lack of an effective treatment, AD has become a major public health problem in the USA and worldwide. Due to variation in age-at-onset, AD is classified into early-onset (< 60 years) and late-onset (≥ 60 years) forms with early-onset accounting for only 5-10% of all cases. With the exception of a small number of early-onset cases that are afflicted because of high penetrant single gene mutations in APP, PSEN1, and PSEN2 genes, AD is genetically heterogeneous, especially the late-onset form having a polygenic or oligogenic risk inheritance. Since the identification of APOE as the most significant risk factor for late-onset AD in 1993, the path to the discovery of additional AD risk genes had been arduous until 2009 when the use of large genome-wide association studies opened up the discovery gateways that led the identification of ~ 95 additional risk loci from 2009 to early 2022. This article reviews the history of AD genetics followed by the potential molecular pathways and recent application of functional genomics methods to identify the causal AD gene(s) among the many genes that reside within a single locus. The ultimate goal of integrating genomics and functional genomics is to discover novel pathways underlying the AD pathobiology in order to identify drug targets for the therapeutic treatment of this heterogeneous disorder.
Identifiants
pubmed: 34935119
doi: 10.1007/s13311-021-01152-0
pii: 10.1007/s13311-021-01152-0
pmc: PMC9130391
doi:
Types de publication
Journal Article
Review
Research Support, N.I.H., Extramural
Langues
eng
Sous-ensembles de citation
IM
Pagination
152-172Subventions
Organisme : NIA NIH HHS
ID : P30 AG066468
Pays : United States
Informations de copyright
© 2021. The Author(s).
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