To determine whether apolipoprotein E epsilon 2 (APOE-epsilon 2) affec
ts neuropathology in aging and Alzheimer's disease (AD), we compared b
eta-amyloid plaque (A beta P) and neurofibrillary tangle densities, ne
uropil thread formation, and amyloid angiopathy in five APOE-epsilon 2
/3 AD patients, five APOE-epsilon 3/3 AD patients, five APOE-epsilon 2
/3 control patients, and five APOE-epsilon 3/3 control patients. We ex
amined the (frontal and parietal) neocortex, hippocampus, entorhinal c
ortex, 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; eve
n 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 inf
luence pathologic phenotype in some aged normal and AD populations.