Cerebrovascular contributions to aging and Alzheimer's disease in Down syndrome

Abstract

Down syndrome (DS) is a common cause of intellectual disability and is also associated with early age of onset of Alzheimer's disease (AD). Due to an extra copy of chromosome 21, most adults over 40years old with DS have beta-amyloid plaques as a result of overexpression of the amyloid precursor protein. Cerebrovascular pathology may also be a significant contributor to neuropathology observed in the brains of adults with DS. This review describes the features of cardiovascular dysfunction and cerebrovascular pathology in DS that may be modifiable risk factors and thus targets for interventions. We will describe cerebrovascular pathology, the role of co-morbidities, imaging studies indicating vascular pathology and the possible consequences. It is clear that our understanding of aging and AD in people with DS will benefit from further studies to determine the role that cerebrovascular dysfunction contributes to cognitive health. This article is part of a Special Issue entitled: Vascular Contributions to Cognitive Impairment and Dementia edited by M. Paul Murphy, Roderick A. Corriveau and Donna M. Wilcock.

Keywords: Beta-amyloid; Cerebral amyloid angiopathy; Hypertension; Hypotension; Microhemorrhages; Moyamoya; Sleep apnea; Stroke.

Copyright © 2015 Elsevier B.V. All rights reserved.

Figures

Fig. 1

Cerebrovascular neuropathology in DS. (A) Beta-amyloid 1-42 immunostaining of the frontal cortex in 67-year old adult with DS and AD shows plaques and significant CAA in multiple small vessels (arrows). (B) Beta-amyloid 1-40 shows a different pattern with fewer plaques being labeled with CAA appearing more prominent, particularly in vessels (arrows). (C) Prussian blue staining of a 58-year old with DS and AD shows significant numbers of microhemorrhages (blue). T2* weighted MR images in a 60-year old male with DS, who is currently nondemented over a 2-year time interval, shows significant CAA in the occipital cortex that is progressively getting worse (white arrows) (images courtesy of Dr. David Powell, University of Kentucky).