TY - JOUR
T1 - Alzheimer's disease risk genes and mechanisms of disease pathogenesis
AU - Karch, Celeste M.
AU - Goate, Alison M.
N1 - Publisher Copyright:
© 2015 Society of Biological Psychiatry.
PY - 2015/1/1
Y1 - 2015/1/1
N2 - We review the genetic risk factors for late-onset Alzheimer's disease (AD) and their role in AD pathogenesis. More recent advances in understanding of the human genome - technologic advances in methods to analyze millions of polymorphisms in thousands of subjects - have revealed new genes associated with AD risk, including ABCA7, BIN1, CASS4, CD33, CD2AP, CELF1, CLU, CR1, DSG2, EPHA1, FERMT2, HLA-DRB5-DBR1, INPP5D, MS4A, MEF2C, NME8, PICALM, PTK2B, SLC24H4-RIN3, SORL1, and ZCWPW1. Emerging technologies to analyze the entire genome in large data sets have also revealed coding variants that increase AD risk: PLD3 and TREM2. We review the relationship between these AD risk genes and the cellular and neuropathologic features of AD. Understanding the mechanisms underlying the association of these genes with risk for disease will provide the most meaningful targets for therapeutic development to date.
AB - We review the genetic risk factors for late-onset Alzheimer's disease (AD) and their role in AD pathogenesis. More recent advances in understanding of the human genome - technologic advances in methods to analyze millions of polymorphisms in thousands of subjects - have revealed new genes associated with AD risk, including ABCA7, BIN1, CASS4, CD33, CD2AP, CELF1, CLU, CR1, DSG2, EPHA1, FERMT2, HLA-DRB5-DBR1, INPP5D, MS4A, MEF2C, NME8, PICALM, PTK2B, SLC24H4-RIN3, SORL1, and ZCWPW1. Emerging technologies to analyze the entire genome in large data sets have also revealed coding variants that increase AD risk: PLD3 and TREM2. We review the relationship between these AD risk genes and the cellular and neuropathologic features of AD. Understanding the mechanisms underlying the association of these genes with risk for disease will provide the most meaningful targets for therapeutic development to date.
KW - Alzheimers Disease
KW - Amyloid Precursor Protein
KW - Cholesterol Metabolism
KW - Endocytosis
KW - Genome-Wide Association Studies
KW - Immune Response
UR - http://www.scopus.com/inward/record.url?scp=84920703987&partnerID=8YFLogxK
U2 - 10.1016/j.biopsych.2014.05.006
DO - 10.1016/j.biopsych.2014.05.006
M3 - Review article
C2 - 24951455
AN - SCOPUS:84920703987
SN - 0006-3223
VL - 77
SP - 43
EP - 51
JO - Biological Psychiatry
JF - Biological Psychiatry
IS - 1
ER -