11 - Hereditary forms of cerebrovascular amyloidosis

Summary

The most frequent forms of amyloidoses are those localized to the central nervous system (CNS). Both vascular and parenchymal amyloid lesions in Alzheimer's disease (AD) are composed of self-aggregates of the Aβ peptide, a processing product of a larger precursor protein (APP) codified by a single gene located on chromosome 21. Mutations located within the Aβ sequence are, with few exceptions, associated with vascular compromise. This chapter describes these mutations, their clinical phenotypes as well as associated neuropathological abnormalities. The presence of familial forms of cerebral amyloid angiopathy (CAA), either related to genetic variants of Aβ or to non-Aβ CAA proteins, provides unique paradigms to examine the role of amyloid in the mechanism of disease pathogenesis, and to dissect the link between vascular and parenchymal amyloid deposition and their differential contribution to neurodegeneration. The neuropathological similarities among CAA-related entities suggest mechanistic pathways leading to cell toxicity,cellular dysfunction and death.