X11α haploinsufficiency enhances Aβ amyloid deposition in Alzheimer's disease transgenic mice

Inderjeet Saluja; Henry Paulson; Ashwin Gupta; R. Scott Turner

Neurobiology of Disease (Oct 2009)

X11α haploinsufficiency enhances Aβ amyloid deposition in Alzheimer's disease transgenic mice

Inderjeet Saluja,
Henry Paulson,
Ashwin Gupta,
R. Scott Turner

Affiliations

Inderjeet Saluja: Department of Neurology, University of Michigan, USA; Corresponding authors. H. Paulson is to be contacted at Neurology 4001 BSRB, 109 Zina Pitcher Place, Ann Arbor, MI 48109, USA. Fax: +1 734 763 7686. I. Saluja, VAMC GRECC 11G, 2215 Fuller Road, Ann Arbor, MI 48105, USA. Fax: +1 734 845 3298.
Henry Paulson: Department of Neurology, University of Michigan, USA; Corresponding authors. H. Paulson is to be contacted at Neurology 4001 BSRB, 109 Zina Pitcher Place, Ann Arbor, MI 48109, USA. Fax: +1 734 763 7686. I. Saluja, VAMC GRECC 11G, 2215 Fuller Road, Ann Arbor, MI 48105, USA. Fax: +1 734 845 3298.
Ashwin Gupta: Department of Neurology, University of Michigan, USA
R. Scott Turner: Department of Neurology, University of Michigan, USA; VA GRECC, Ann Arbor, MI, USA

Journal volume & issue: Vol. 36, no. 1
pp. 162 – 168

Abstract

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The neuronal adaptor protein X11α/mint-1/APBA-1 binds to the cytoplasmic domain of the amyloid precursor protein (APP) to modulate its trafficking and metabolism. We investigated the consequences of reducing X11α in a mouse model of Alzheimer's disease (AD). We crossed hAPPswe/PS-1ΔE9 transgenic (AD tg) mice with X11α heterozygous knockout mice in which X11α expression is reduced by approximately 50%. The APP C-terminal fragments C99 and C83, as well as soluble Aβ40 and Aβ42, were increased significantly in brain of X11α haploinsufficient mice. Aβ/amyloid plaque burden also increased significantly in the hippocampus and cortex of one year old AD tg/X11α (+/−) mice compared to AD tg mice. In contrast, the levels of sAPPα and sAPPβ were not altered significantly in AD tg/X11α (+/−) mice. The increased neuropathological indices of AD in mice expressing reduced X11α suggest a normal suppressor role for X11α on CNS Aβ/amyloid deposition.

Published in Neurobiology of Disease

ISSN: 0969-9961 (Print); 1095-953X (Online)
Publisher: Elsevier
Country of publisher: United States
LCC subjects: Medicine: Internal medicine: Neurosciences. Biological psychiatry. Neuropsychiatry
Website: https://www.journals.elsevier.com/neurobiology-of-disease

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