Natural oligomers of the amyloid-β protein specifically disrupt cognitive function

James P. Cleary, Dominic M. Walsh, Jacki J Hofmeister, Ganesh M. Shankar, Michael A Kuskowski, Dennis J. Selkoe, Karen H Ashe

Research output: Contribution to journalArticle

1330 Citations (Scopus)

Abstract

A central unresolved problem in research on Alzheimer disease is the nature of the molecular entity causing dementia. Here we provide the first direct experimental evidence that a defined molecular species of the amyloid-β protein interferes with cognitive function. Soluble oligomeric forms of amyloid-β, including trimers and dimers, were both necessary and sufficient to disrupt learned behavior in a manner that was rapid, potent and transient; they produced impaired cognitive function without inducing permanent neurological deficits. Although β-amyloidosis has long been hypothesized to affect cognition, the abnormally folded protein species associated with this or any other neurodegenerative disease has not previously been isolated, defined biochemically and then specifically characterized with regard to its effects on cognitive function. The biochemical isolation of discrete amyloid-β moieties with pathophysiological properties sets the stage for a new approach to studying the molecular mechanisms of cognitive impairment in Alzheimer disease and related neurodegenerative disorders.

Original languageEnglish (US)
Pages (from-to)79-84
Number of pages6
JournalNature Neuroscience
Volume8
Issue number1
DOIs
StatePublished - Jan 1 2005

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Amyloidogenic Proteins
Cognition
Amyloid
Neurodegenerative Diseases
Alzheimer Disease
Amyloidosis
Dementia
Research
Proteins

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Natural oligomers of the amyloid-β protein specifically disrupt cognitive function. / Cleary, James P.; Walsh, Dominic M.; Hofmeister, Jacki J; Shankar, Ganesh M.; Kuskowski, Michael A; Selkoe, Dennis J.; Ashe, Karen H.

In: Nature Neuroscience, Vol. 8, No. 1, 01.01.2005, p. 79-84.

Research output: Contribution to journalArticle

Cleary, James P. ; Walsh, Dominic M. ; Hofmeister, Jacki J ; Shankar, Ganesh M. ; Kuskowski, Michael A ; Selkoe, Dennis J. ; Ashe, Karen H. / Natural oligomers of the amyloid-β protein specifically disrupt cognitive function. In: Nature Neuroscience. 2005 ; Vol. 8, No. 1. pp. 79-84.
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