Epidemiological, clinical, and neuropathological study of apolipoprotein E genotype in Alzheimer's disease.
Our studies of the APOE genotype in AD confirm a strong association of the epsilon 4 allele with development of AD and a decreased risk associated with epsilon 2. From a clinical/neuropathological perspective, the major effects of APOE epsilon 4 are to lower the age of onset and to increase the amount of A beta deposit in the brain. Neither rate of progression nor number of neurofibrillary tangles were affected. We also carried out a longitudinal population-based assessment of the APOE genotype to determine the risk for developing cognitive impairment of someone in the general population based on APOE genotype. APOE epsilon 4 carried about 1.4-fold increased risk, and APOE epsilon 2 about 1.7-fold decreased risk. Thus, inheritance of APOE epsilon 4 is a major biological risk factor for AD, but it has limited utility as a prognostic indicator for development of dementia in an individual.
Hyman
B T
BT
Neurology Service, Massachusetts General Hospital, Boston 02114, USA.
Gomez-Isla
T
T
Rebeck
G W
GW
Briggs
M
M
Chung
H
H
West
H L
HL
Greenberg
S
S
Mui
S
S
Nichols
S
S
Wallace
R
R
Growdon
J H
JH
D017668:Age of Onset; D000368:Aged; D000544:Alzheimer Disease / Q000175:diagnosis / Q000235:genetics* / Q000473:pathology; D053327:Apolipoprotein E4; D001057:Apolipoproteins E / Q000235:genetics*; D001921:Brain / Q000473:pathology; D005838:Genotype; D006801:Humans; D007484:Iowa; D008137:Longitudinal Studies; D008404:Massachusetts; D011379:Prognosis; D012307:Risk Factors
D053327:Apolipoprotein E4; D001057:Apolipoproteins E