Apolipoprotein E-epsilon 2 and Alzheimer's disease: genotype influences pathologic phenotype.
To determine whether apolipoprotein E epsilon 2 (APOE-epsilon 2) affects neuropathology in aging and Alzheimer's disease (AD), we compared beta-amyloid plaque (A beta P) and neurofibrillary tangle densities, neuropil thread formation, and amyloid angiopathy in five APOE-epsilon 2/3 AD patients, five APOE-epsilon 3/3 AD patients, five APOE-epsilon control patients, and five APOE-epsilon 3/3 control patients. We examined the (frontal and parietal) neocortex, hippocampus, entorhinal cortex, and cerebellum and found A beta P densities to be lower (t = 3.121, p = 0.011) in the cortex of APOE-epsilon 2/3 AD patients than in APOE-epsilon 3/3 AD patients. Amyloid angiopathy was also less in APOE-epsilon 2/3 patients than in APOE-3/3 patients (U = 4.500, p = 0.027). Control APOE-epsilon 2/3 brains had little AD-related pathology; even our 102-year-old control case showed few A beta Ps compared with the elderly APOE-epsilon 3/3 cases. The APOE-epsilon 2/3 genotype may influence pathologic phenotype in some aged normal and AD populations.
Lippa
C F
CF
Department of Neurology, Allegheny University-East Falls, Philadelphia, PA 12129, USA.
Smith
T W
TW
Saunders
A M
AM
Hulette
C
C
Pulaski-Salo
D
D
Roses
A D
AD
D000368:Aged; D000483:Alleles; D000544:Alzheimer Disease / Q000235:genetics / Q000378:metabolism / Q000473:pathology*; D016229:Amyloid beta-Peptides / Q000378:metabolism; D053329:Apolipoprotein E2; D053318:Apolipoprotein E3; D001057:Apolipoproteins E / Q000235:genetics*; D001921:Brain / Q000378:metabolism / Q000473:pathology; D005260:Female; D005838:Genotype; D006801:Humans; D008297:Male; D008875:Middle Aged; D016874:Neurofibrillary Tangles / Q000473:pathology*; D010641:Phenotype
D016229:Amyloid beta-Peptides; D053329:Apolipoprotein E2; D053318:Apolipoprotein E3; D001057:Apolipoproteins E