Vascular pathology in ApoE3,3 and ApoE4,4 dementia

Inheritance of the lipid transport molecule, ApoE4, is associated with increased risk of Alzheimer's Disease (AD). ApoE4 is also associated with increased vascular amyloid deposits and vascular dementia. Imaging studies have shown increased microvascular disease in sporadic ApoE3 AD, but pathologically, these cases lack vascular amyloid. In order to examine vascular pathology, we undertook a comparative analysis of ApoE3,3 and ApoE4,4 dementia. Ten ApoE3,3 and ten ApoE4,4 AD brains as well as 5 normal controls and 5 possible AD cases were selected and matched for duration of disease. The AD cases met NIA Reagan Institute criteria for the diagnosis of Alzheimer's Disease. Sections of frontal and parietal cortex were stained with antibodies against beta A4 ApoE Cystatin C Collagen IV and smooth muscle actin. We found a higher load of beta A4 ApoE and Collagen IV in cortical vessels in patients with ApoE4,4 compared to patients with ApoE3,3 Alzheimer's Disease. Atrophic vessels were more common in patients with the ApoE4,4 genotype. Greater immunoreactivity for ApoE and Collagen IV in the ApoE4,4 group could be explained by co-existent cerebral amyloid angiopathy. We then performed more extensive analysis using smooth muscle actin (SMA) immunohistochemistry. This staining was quantified using image analysis. We found increased SMA density in arachnoid brood vessels compared to the gray and white matter in all cases. We also found significantly higher vascular smooth muscle actin density in ApoE3,3 Alzheimer's Disease and in normal cases when compared to ApoE4,4 AD. ApoE4 and amyloid deposition may play a role in decreasing vascular smooth muscle actin density in cortical blood vessels in patients with Alzheimer's Disease. These pathologies could possibly contribute to blood brain barrier abnormalities in patients with ApoE4 Alzheimer's Disease.