David A Drachman1, Thomas W Smith2, Bassam Alkamachi3, Kevin Kane4. 1. Department of Neurology, University of Massachusetts Medical School, Worcester, MA, USA. 2. Department of Neurology, University of Massachusetts Medical School, Worcester, MA, USA; Department of Pathology, University of Massachusetts Medical School, USA. Electronic address: thomas.smith@umassmemorial.org. 3. Theranostix Laboratory, Beltsville, MD, USA. 4. Health Statistics and Geography Lab, Division of Preventive and Behavioral Medicine, University of Massachusetts Medical School, USA.
Abstract
INTRODUCTION: The 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. METHODS: We 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. RESULTS: Microvascular numbers and endothelial integrity were significantly diminished in DS brains compared with controls and were similar to AD brains. DISCUSSION: People 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.
INTRODUCTION: The 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. METHODS: We 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. RESULTS: Microvascular numbers and endothelial integrity were significantly diminished in DS brains compared with controls and were similar to AD brains. DISCUSSION: People 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.
Authors: Pablo Galeano; María C Leal; Carina C Ferrari; María C Dalmasso; Pamela V Martino Adami; María I Farías; Juan C Casabona; Mariana Puntel; Sonia Do Carmo; Clara Smal; Martín Arán; Eduardo M Castaño; Fernando J Pitossi; A Claudio Cuello; Laura Morelli Journal: Mol Neurobiol Date: 2018-03-26 Impact factor: 5.590
Authors: Fanny M Elahi; Kaitlin B Casaletto; Renaud La Joie; Samantha M Walters; Danielle Harvey; Amy Wolf; Lauren Edwards; Wilfredo Rivera-Contreras; Anna Karydas; Yann Cobigo; Howard J Rosen; Charles DeCarli; Bruce L Miller; Gil D Rabinovici; Joel H Kramer Journal: Alzheimers Dement Date: 2020-01-16 Impact factor: 21.566