Aquaporin expression in the brains of patients with or without cerebral amyloid angiopathy.

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 (AQP4) 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 AQP4 expression compared with the age- and sex-matched controls. Aquaporin 4 immunoreactivity was prominent at the cerebrospinal fluid 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 sex-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.

Cerebral microinfarcts associated with severe cerebral beta-amyloid angiopathy.

Cerebral amyloid angiopathy (CAA) is common in elderly individuals, especially those affected with Alzheimer's disease. Eighteen brains with severe SCAA (SCAA) were compared with 21 brains with mild CAA (MCAA) to investigate whether the presence of SCAA in the brains of demented patients was associated with a higher burden of old microinfarcts than those 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, two-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, two-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.