Amyloid deposition within cerebral vessels, or
cerebral amyloid angiopathy (CAA), is common in advanced age and even more common in
Alzheimer's disease. CAA may be complicated by lobar
intracerebral hemorrhage, while rare kindreds of autosomal dominant CAA also show propensity for
intracerebral hemorrhage, due to germline mutations in specific amyloidogenic precursor
proteins and apparent compromise of structural integrity of the blood vessel wall due to marked
amyloid deposition. The relationship between
cerebral amyloid angiopathy and
cognitive dysfunction, however, is less clear. While
cognitive dysfunction in familial CAA is likely related to prodigious
amyloid deposits and vascular
luminal compromise (e.g., hereditary
cerebral hemorrhage with angiopathy-Dutch type (
HCHWA-D)),
cerebral amyloid angiopathy with
intracerebral hemorrhage often presents sporadically in cognitively intact elderly patients. Moreover, while about 80% of subjects with
Alzheimer's disease have demonstrable
amyloid beta within blood vessel walls at autopsy, the vast majority of these fail to suffer clinically relevant
intracerebral hemorrhage during life. The remaining 20% manage to progress and die of their disease with virtual no
amyloid within blood vessels. Thus, the role of
amyloid beta deposits in cerebral vessels as regards cognitive function on the one hand, and tendency for
hemorrhage on the other, remain to be resolved for sporadic late onset
Alzheimer's disease and CAA. Recent studies on transgenic APP23 mice suggest a relationship between passive immunization and
amyloid angiopathy-associated
cerebral hemorrhage, although the mechanism of
hemorrhage was unclear from the data presented. We suggest that
amyloid accumulation represents a response to chronic stress, and that the neurodegenerative process occurs at the neuronal level, encompassing oxidative stress and aberrant cell cycle activation. As such, CAA represents tissue homeostasis, such that an abrupt perturbation of this balance (e.g.,
amyloid beta immunization) is deleterious.