A specific amyloid-β protein assembly in the brain impairs memory

Sylvain Lesné, Teng Koh Ming, Linda Kotilinek, Rakez Kayed, Charles G. Glabe, Austin Yang, Michela Gallagher, Karen H. Ashe

Research output: Contribution to journalArticle

2137 Citations (Scopus)

Abstract

Memory function often declines with age1, and is believed to deteriorate initially because of changes in synaptic function rather than loss of neurons2. Some individuals then go on to develop Alzheimer's disease with neurodegeneration. Here we use Tg2576 mice, which express a human amyloid-β precursor protein (APP) variant linked to Alzheimer's disease, to investigate the cause of memory decline in the absence of neurodegeneration or amyloid-β protein amyloidosis. Young Tg2576 mice (<6 months old) have normal memory and lack neuropathology, middle-aged mice (6-14 months old) develop memory deficits without neuronal loss, and old mice (>14 months old) form abundant neuritic plaques containing amyloid-β (refs 3-6). We found that memory deficits in middle-aged Tg2576 mice are caused by the extracellular accumulation of a 56-kDa soluble amyloid-β assembly, which we term Aβ*56 (Aβ star 56). Aβ*56 purified from the brains of impaired Tg2576 mice disrupts memory when administered to young rats. We propose that Aβ*56 impairs memory independently of plaques or neuronal loss, and may contribute to cognitive deficits associated with Alzheimer's disease.

Original languageEnglish (US)
Pages (from-to)352-357
Number of pages6
JournalNature
Volume440
Issue number7082
DOIs
StatePublished - Mar 16 2006
Externally publishedYes

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Serum Amyloid A Protein
Alzheimer Disease
Brain
Amyloid
Amyloidogenic Proteins
Amyloid beta-Protein Precursor
Amyloid Plaques
Memory Disorders
Amyloidosis

ASJC Scopus subject areas

  • General

Cite this

Lesné, S., Ming, T. K., Kotilinek, L., Kayed, R., Glabe, C. G., Yang, A., ... Ashe, K. H. (2006). A specific amyloid-β protein assembly in the brain impairs memory. Nature, 440(7082), 352-357. https://doi.org/10.1038/nature04533

A specific amyloid-β protein assembly in the brain impairs memory. / Lesné, Sylvain; Ming, Teng Koh; Kotilinek, Linda; Kayed, Rakez; Glabe, Charles G.; Yang, Austin; Gallagher, Michela; Ashe, Karen H.

In: Nature, Vol. 440, No. 7082, 16.03.2006, p. 352-357.

Research output: Contribution to journalArticle

Lesné, S, Ming, TK, Kotilinek, L, Kayed, R, Glabe, CG, Yang, A, Gallagher, M & Ashe, KH 2006, 'A specific amyloid-β protein assembly in the brain impairs memory', Nature, vol. 440, no. 7082, pp. 352-357. https://doi.org/10.1038/nature04533
Lesné S, Ming TK, Kotilinek L, Kayed R, Glabe CG, Yang A et al. A specific amyloid-β protein assembly in the brain impairs memory. Nature. 2006 Mar 16;440(7082):352-357. https://doi.org/10.1038/nature04533
Lesné, Sylvain ; Ming, Teng Koh ; Kotilinek, Linda ; Kayed, Rakez ; Glabe, Charles G. ; Yang, Austin ; Gallagher, Michela ; Ashe, Karen H. / A specific amyloid-β protein assembly in the brain impairs memory. In: Nature. 2006 ; Vol. 440, No. 7082. pp. 352-357.
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