Hereditary and Sporadic Forms of Abeta-cerebrovascular Amyloidosis and Relevant Transgenic Mouse Models

Overview

Journal Int J Mol Sci

Publisher MDPI

Specialties Biochemistry
Chemistry
Molecular Biology

Date 2009 May 27

PMID 19468344

Citations 18

Authors

Samir Kumar-Singh

Affiliations

Soon will be listed here.

Abstract

Cerebral amyloid angiopathy (CAA) refers to the specific deposition of amyloid fibrils in the leptomeningeal and cerebral blood vessel walls, often causing secondary vascular degenerative changes. Although many kinds of peptides are known to be deposited as vascular amyloid, amyloid-beta (Abeta)-CAA is the most common type associated with normal aging, sporadic CAA, Alzheimer's disease (AD) and Down's syndrome. Moreover, Abeta-CAA is also associated with rare hereditary cerebrovascular amyloidosis due to mutations within the Abeta domain of the amyloid precursor protein (APP) such as Dutch and Flemish APP mutations. Genetics and clinicopathological studies on these familial diseases as well as sporadic conditions have already shown that CAA not only causes haemorrhagic and ischemic strokes, but also leads to progressive dementia. Transgenic mouse models based on familial AD mutations have also successfully reproduced many of the features found in human disease, providing us with important insights into the pathogenesis of CAA. Importantly, such studies have pointed out that specific vastopic Abeta variants or an unaltered Abeta42/Abeta40 ratio favor vascular Abeta deposition over parenchymal plaques, but higher than critical levels of Abeta40 are also observed to be anti-amyloidogenic. These data would be important in the development of therapies targeting amyloid in vessels.

Citing Articles

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Plasma Amyloid-Beta Levels in a Pre-Symptomatic Dutch-Type Hereditary Cerebral Amyloid Angiopathy Pedigree: A Cross-Sectional and Longitudinal Investigation.

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