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APOE Genotype and Brain Development

APOE Genotype and Brain Development Opinion EDITORIAL John H. Growdon, MD; Bradley T. Hyman, MD, PhD Theobservationthatinheritance of the apolipoprotein E (APOE) of interest that were determined by prior experience in AD, so ε4 allele predisposes dramatically to Alzheimer disease (AD) was a certain circularity in the logic is inevitable. Also, by the na- first reported in 1993 and has been replicated in hundreds of ture of the study, multiple possible measurements are com- studies thereafter. It is one of the most robust genetic associa- pared, and most results do not hold up to multiple compari- tions with common disease discovered in all of medicine, yet son testing, making this more of a hypothesis-generating data despite 20 years of research, the reason that APOE ε4 has such set than a confirmed set of observations. The population ex- a profound increase of risk in AD remains uncertain. Several facts amined was not selected, but the percentage of ε4 carriers was are clear: (1) the APOE ε4 genotype predisposes toward AD pa- substantially higher than one would have expected in the gen- thology, primarily with amy- eral population, raising a concern about some underlying bias loid deposits ; (2) the predis- variable in selection for the http://www.deepdyve.com/assets/images/DeepDyve-Logo-lg.png JAMA Neurology American Medical Association

APOE Genotype and Brain Development

JAMA Neurology , Volume 71 (1) – Jan 1, 2014

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Publisher
American Medical Association
Copyright
Copyright 2014 American Medical Association. All Rights Reserved. Applicable FARS/DFARS Restrictions Apply to Government Use.
ISSN
2168-6149
eISSN
2168-6157
DOI
10.1001/jamaneurol.2013.5200
pmid
24276019
Publisher site
See Article on Publisher Site

Abstract

Opinion EDITORIAL John H. Growdon, MD; Bradley T. Hyman, MD, PhD Theobservationthatinheritance of the apolipoprotein E (APOE) of interest that were determined by prior experience in AD, so ε4 allele predisposes dramatically to Alzheimer disease (AD) was a certain circularity in the logic is inevitable. Also, by the na- first reported in 1993 and has been replicated in hundreds of ture of the study, multiple possible measurements are com- studies thereafter. It is one of the most robust genetic associa- pared, and most results do not hold up to multiple compari- tions with common disease discovered in all of medicine, yet son testing, making this more of a hypothesis-generating data despite 20 years of research, the reason that APOE ε4 has such set than a confirmed set of observations. The population ex- a profound increase of risk in AD remains uncertain. Several facts amined was not selected, but the percentage of ε4 carriers was are clear: (1) the APOE ε4 genotype predisposes toward AD pa- substantially higher than one would have expected in the gen- thology, primarily with amy- eral population, raising a concern about some underlying bias loid deposits ; (2) the predis- variable in selection for the

Journal

JAMA NeurologyAmerican Medical Association

Published: Jan 1, 2014

References