Severe cerebral amyloid angiopathy in Alzheimer's disease is associated with frequent old microinfarcts

Abstract

To investigate whether the presence of severe cerebral amyloid angiopathy (CAA) in Alzheimer's disease (AD) was associated with a higher prevalence of old microinfarcts (OMIs) than in AD without significant CAA, 6 AD brains with severe CAA were selected, together with 12 age‐matched AD brains without significant CAA, from the Alzheimer's Disease Research Center Tissue Bank. Immunohistochemistry for CD68 was employed to highlight ≤5 mm foci of macrophage‐infiltrated tissue destruction (i.e. OMIs) in formalin‐fixed paraffin‐embedded tissue blocks taken from various regions of the cerebral cortex/white matter and cerebellum (range 13–21, mean 16.3 blocks per brain in the AD/CAA group; range 7–21, mean 14.7 blocks per brain in the AD group; p = 0.39, 2‐tailed Student's t‐Test). OMIs, manually counted by light microscopy, were observed in all of 6 AD/CAA brains, and in 2 out of 12 AD brains (p = 0.0015, 2‐tailed Fisher's Exact Test). The number of OMIs per block ranged from 0.14 to 1.76 (mean 0.74) in the AD/CAA group, and from 0 to 0.12 (mean 0.02) in the AD group (p = 0.02, 1‐tailed Student's t‐Test). Using Perl's iron staining, old microhemorrhages were occasionally seen in both groups. In conclusion, OMIs are frequent in AD with severe CAA, which may contribute to a vascular component of cognitive impairment. This work was supported by the grants P50 AG16570, P01 AG12435 and the Sarkaria Chair in Diagnostic Medicine (H.V.V.).