TY - JOUR
T1 - A Quarter Century of APOE and Alzheimer's Disease
T2 - Progress to Date and the Path Forward
AU - Belloy, Michaël E.
AU - Napolioni, Valerio
AU - Greicius, Michael D.
N1 - Publisher Copyright:
© 2019 Elsevier Inc.
PY - 2019/3/6
Y1 - 2019/3/6
N2 - Alzheimer's disease (AD) is considered a polygenic disorder. This view is clouded, however, by lingering uncertainty over how to treat the quasi “monogenic” role of apolipoprotein E (APOE). The APOE4 allele is not only the strongest genetic risk factor for AD, it also affects risk for cardiovascular disease, stroke, and other neurodegenerative disorders. This review, based mostly on data from human studies, ranges across a variety of APOE-related pathologies, touching on evolutionary genetics and risk mitigation by ethnicity and sex. The authors also address one of the most fundamental question pertaining to APOE4 and AD: does APOE4 increase AD risk via a loss or gain of function? The answer will be of the utmost importance in guiding future research in AD.
AB - Alzheimer's disease (AD) is considered a polygenic disorder. This view is clouded, however, by lingering uncertainty over how to treat the quasi “monogenic” role of apolipoprotein E (APOE). The APOE4 allele is not only the strongest genetic risk factor for AD, it also affects risk for cardiovascular disease, stroke, and other neurodegenerative disorders. This review, based mostly on data from human studies, ranges across a variety of APOE-related pathologies, touching on evolutionary genetics and risk mitigation by ethnicity and sex. The authors also address one of the most fundamental question pertaining to APOE4 and AD: does APOE4 increase AD risk via a loss or gain of function? The answer will be of the utmost importance in guiding future research in AD.
KW - AD
KW - Alzheimer's disease
KW - anti-sense oligonucleotide
KW - APOE
KW - Apolipoprotein E
KW - ASO
KW - cardiovascular disease
KW - ethnicity
KW - evolutionary genetics
KW - gene-based therapy
KW - neurodegenerative disease
KW - pleiotropy
KW - sex
UR - http://www.scopus.com/inward/record.url?scp=85061622859&partnerID=8YFLogxK
U2 - 10.1016/j.neuron.2019.01.056
DO - 10.1016/j.neuron.2019.01.056
M3 - Review article
C2 - 30844401
AN - SCOPUS:85061622859
SN - 0896-6273
VL - 101
SP - 820
EP - 838
JO - Neuron
JF - Neuron
IS - 5
ER -