Apolipoprotein E-E4 Alleles in Cerebral Amyloid Angiopathy and Cerebrovascular Pathology Associated with Alzheimer's Disease

The presence of apolipoprotein E-e4 (APOE-e4) allele has been implicated as a risk factor for Alzheimer's disease (AD). We examined the frequencies of APOE-e4 alleles in age-matched controls and subgroups of 190 AD subjects exhibiting cerebral amyloid angiopathy (CAA) and otherfrequently associated lesions. CAA was evident
in 96% of the AD subjects, which were divided into two groups, one bearing mild or no apparent CAA and the other with moderate to
severe CAA. APOE-e4 allele frequency (48%) in the latter advanced CAA group was six times higher than in those who exhibited mild CAA. .........

Figure 1. Inininocytochemnical localizationt of A,B protein in cerebral vessels ol'AD subjects miiatched/br age and dinrationn uf/disease. A: Intensely
staininig concentric patterns and focal deposits ofAP3 in isolated initracortical microvessels from a 65-year-old AD suibject with E4/E4 geniotlpe. Note
deposition along whole vessel len?gth antdfinie deposits ofAP3 in capillaries (arrows). B: Conitrol sub/ject With E2/E3 genotype shooing lack ofspecific
imiunoreactivity. Prcparsationis itmmuzostained with preimniune serutni gale similar backgrounld stainingi. C: A,B immnnonoreactivejocal deposits
(arrows) inz a tinlcrovesselfromi a 69-year-old AD subject Uith E,31E3 genzotpe inidicatinig miinimal CAA. D: Severe CAA (grade 3) represented bhy A,B
immunoreactiity in mneninigeal anid intracortical vez;ssels. Occipital cortex tissuie section from an AD .subject with E 3/E4 genotype. SpecLic stainin1Fg uwas
liot evident eithbe in tissuefifom age-matched controls wvith nio CAA. bhen tissue from AD subjects wa.s inicubated in the absence of'antibody, or in
the presence oj'preiinimune serum or- anztibody (3160) absorbed uith A,B pepticle. Nuclei are rei'ealed by hbematoxilin counterstain; banrs. 50 p.ni (A
B, and C) anid 20 Ani (D).