NDLI: Pyroglutamate-3 amyloid-ß deposition in the brains of humans, non-human primates, canines, and Alzheimer disease-like transgenic mouse models.

Content Provider	World Health Organization (WHO)-Global Index Medicus
Author	Frost, Jeffrey L. Le, Kevin X. Cynis, Holger Ekpo, Elizabeth Kleinschmidt, Martin Palmour, Roberta M. Ervin, Frank R. Snigdha, Shikha Cotman, Carl W. Saido, Takaomi C. Vassar, Robert J. St George-Hyslop, Peter Ikezu, Tsuneya Schilling, Stephan Demuth, Hans-Ulrich Lemere, Cynthia A.
Description	Country affiliation: United States Author Affiliation: Frost JL ( Center for Neurologic Diseases, Department of Neurology, Brigham and Women's Hospital, Harvard Medical School, Boston, Massachusetts, USA.)
Abstract	Amyloid-ß (Aß) peptides, starting with pyroglutamate at the third residue (pyroGlu-3 Aß), are a major species deposited in the brain of Alzheimer disease (AD) patients. Recent studies suggest that this isoform shows higher toxicity and amyloidogenecity when compared to full-length Aß peptides. Here, we report the first comprehensive and comparative IHC evaluation of pyroGlu-3 Aß deposition in humans and animal models. PyroGlu-3 Aß immunoreactivity (IR) is abundant in plaques and cerebral amyloid angiopathy of AD and Down syndrome patients, colocalizing with general Aß IR. PyroGlu-3 Aß is further present in two nontransgenic mammalian models of cerebral amyloidosis, Caribbean vervets, and beagle canines. In addition, pyroGlu-3 Aß deposition was analyzed in 12 different AD-like transgenic mouse models. In contrast to humans, all transgenic models showed general Aß deposition preceding pyroGlu-3 Aß deposition. The findings varied greatly among the mouse models concerning age of onset and cortical brain region. In summary, pyroGlu-3 Aß is a major species of ß-amyloid deposited early in diffuse and focal plaques and cerebral amyloid angiopathy in humans and nonhuman primates, whereas it is deposited later in a subset of focal and vascular amyloid in AD-like transgenic mouse models. Given the proposed decisive role of pyroGlu-3 Aß peptides for the development of human AD pathology, this study provides insights into the usage of animal models in AD studies.
File Format	HTM / HTML
ISSN	00029440
e-ISSN	15252191
DOI	10.1016/j.ajpath.2013.05.005
Journal	The American Journal of Pathology
Issue Number	2
Volume Number	183
Language	English
Publisher	Elsevier (on behalf of the American Society for Investigative Pathology)
Publisher Date	2013-08-01
Publisher Place	United States
Access Restriction	Open
Subject Keyword	Immunohistochemistry Research Support, N.i.h., Extramural Brain Research Support, Non-u.s. Gov't Down Syndrome Plaque, Amyloid Cercopithecus Aethiops Disease Models, Animal Amyloid Beta-peptides Mice, Transgenic Discipline Pathology Alzheimer Disease Metabolism Pathology Animals Cerebral Amyloid Angiopathy Amyloid Beta-protein Precursor Mice Pyrrolidonecarboxylic Acid Age Of Onset
Content Type	Text
Resource Type	Article
Subject	Pathology and Forensic Medicine

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Pyroglutamate-3 Amyloid-β Deposition in the Brains of Humans, Non-Human Primates, Canines, and Alzheimer Disease–Like Transgenic Mouse Models

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