NEUROLOGICAL INFECTION AND INFLAMMATION

Contribution of CAA to Alzheimer’s disease In patients with Alzheimer’s disease (AD), focal and diffuse ischaemic abnormalities of the cerebral white matter can be demonstrated neuropathologically1–3 and neuroradiologically.4–8 The focal lesions have been shown to contribute to motor and neuropsychiatric manifestations of AD,9–12 and the more widespread or diffuse abnormalities to impaired cognition.1314 In some series, ischaemic cerebral lesions in AD have been more frequent in patients homozygous or heterozygous for the epsilon 4 (e4) allele of the apolipoprotein E gene ( APOE ),15–17 but other studies have found no such association,18–21 Studies of the relation between white matter disease in patients with AD or probable AD, and the systemic manifestations of arteriosclerotic vascular disease, have yielded inconsistent findings.11121–24 Several observations implicate cerebral amyloid angiopathy (CAA) as the probable cause of much of the white matter damage in AD. The vascular deposition of amyloid β protein (Aβ) is much more frequent and tends to be much more severe in patients with AD than in age-matched controls.25–29 Furthermore, CAA is a well documented risk factor for cerebral infarction1630–32 and for focal and diffuse white matter ischaemic lesions.33–36 The mechanisms whereby CAA may cause ischaemic damage to the white matter probably include a combination of luminal stenosis, endothelial damage, basement membrane thickening, thrombosis, loss of autoregulation, and vasospasm.37–40 Because evidence of the involvement of CAA in AD is largely based on post-mortem studies, which are by their nature skewed towards end stage disease, it could be argued that any contribution of CAA may be confined to the terminal stages of …