Cerebral amyloid angiopathy (CAA) is common in elderly individuals, especially those affected with Alzheimer's disease. To investigate whether the presence of severe CAA (SCAA) in the brains of demented patients was associated with a higher burden of old microinfarcts than those with mild CAA (MCAA), 18 brains with SCAA were compared to 21 brains with MCAA. Immunohistochemistry for CD68 was employed to highlight old microinfarcts in tissue blocks from various brain regions. Old microinfarcts, manually counted by light microscopy, were present in 14 of 18 SCAA brains, and in 7 of 21 MCAA brains (P = 0.01, 2-tailed Fisher’s exact test). The average number of old microinfarcts across geographic regions in each brain ranged from 0 to 1.95 (mean rank 24.94, sum of ranks 449) in the SCAA group, and from 0 to 0.35 (mean rank 15.76, sum of ranks 331) in the MCAA group (P = 0.008, 2-tailed Mann-Whitney U test). Frequent old microinfarcts in demented individuals with severe CAA may contribute a vascular component to the cognitive impairment in these patients.

Aquaporins have recently been identified as protein channels involved in water transport. These channels may play a role in the edema formation and alterations in microvascular function observed in Alzheimer disease (AD) and cerebral amyloid angiopathy (CAA). We investigated the expression of aquaporin 1 (AQP1) and aquaporin 4 (AQP 4) in 24 human autopsy brains consisting of 18 with AD and varying degrees of CAA, and 6 with no pathologic abnormalities using immunohistochemistry. In cases of AD and CAA there was enhanced AQP 4 expression compared to age- and gender-matched controls. Aquaporin 4 immunoreactivity was prominent at CSF and brain interfaces, including subpial, subependymal, pericapillary and periarteriolar spaces. Aquaporin 1 expression in AD and CAA cases was not different from that in age- and gender-matched controls. Double-labeling studies demonstrated that both AQP1 and 4 were localized to astrocytes. Both enhanced AQP4 expression and its unique staining pattern suggest that these proteins may be important in the impaired water transport observed in AD and CAA.

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.).