• David A Drachman, Thomas W Smith, Bassam Alkamachi, and Kevin Kane.
• Department of Neurology, University of Massachusetts Medical School, Worcester, MA, USA.
• Alzheimers Dement. 2017 Dec 1; 13 (12): 1389-1396.

IntroductionThe mechanism triggering degeneration in Alzheimer's disease (AD) remains uncertain. Therapeutic failure following amyloid β (Aβ) removal casts doubt on amyloid neurotoxicity per se as the primary cause of AD. Impaired microvascular function has been suggested as an alternative etiology. People with Down syndrome (DS) develop Alzheimer's pathology, but whether microvascular impairment also occurs in DS (as in AD) is unknown.MethodsWe examined brain microvasculature in five DS subjects with AD-type histopathology, seven AD cases, and seven controls without AD-type pathology. We counted microvessels in five anatomic regions and assessed endothelial integrity by CD31 immunohistochemistry.ResultsMicrovascular numbers and endothelial integrity were significantly diminished in DS brains compared with controls and were similar to AD brains.DiscussionPeople with DS and trisomy 21 produce a large amount of Aβ. If Alzheimer's pathology occurred in DS without microvascular loss or endothelial impairment, a direct neurotoxic Aβ mechanism would be supported and microvascular impairment rejected. The observation of microvascular impairment in DS with Alzheimer's disease changes fails to reject the microvascular hypothesis and provides some support for this potential mechanism of injury.Copyright © 2017 the Alzheimer's Association. Published by Elsevier Inc. All rights reserved.

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