Cerebral amyloid angiopathy in Alzheimer disease is associated with apolipoprotein E4 and cortical neuron loss

Pathological correlations were sought between cerebral amyloid angiopathy ( CAA) and other classical neurodegenerative changes in 101 consecutive cases of autopsy-confirmed Alzheimer disease (AD). Some degree of CAA was found in at least one area of the brain in 81% of the cases; severe CAA was found in at least one brain region in 29% of the cases. In a subset of 42 cases for which genomic DNA was available, greater severity of CAA was associated more with cases that were homozygous for apolipoprotein epsilon 4 than in cases with only one or no epsilon 4 alleles (Fisher's exact test, p = 0.005 ). In all brain regions, severity of CAA was inversely correlated with numb ers of neurons. This correlation was statistically significant in the tempo ral lobe (r = -0.29, p = 0.004) and the frontal lobe (r = -0.22, p = 0.02). Our findings suggest that two factors may modify the severity of AD pathol ogy: Apolipoprotein E4 may accentuate the vascular deposition of beta-amylo id, and severe CAA may accelerate neuronal loss.