Abstract
The neuronal adaptor protein X11alpha/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 X11alpha in a mouse model of Alzheimer's disease (AD). We crossed hAPPswe/PS-1DeltaE9 transgenic (AD tg) mice with X11alpha heterozygous knockout mice in which X11alpha expression is reduced by approximately 50%. The APP C-terminal fragments C99 and C83, as well as soluble Abeta40 and Abeta42, were increased significantly in brain of X11alpha haploinsufficient mice. Abeta/amyloid plaque burden also increased significantly in the hippocampus and cortex of one year old AD tg/X11alpha (+/-) mice compared to AD tg mice. In contrast, the levels of sAPPalpha and sAPPbeta were not altered significantly in AD tg/X11alpha (+/-) mice. The increased neuropathological indices of AD in mice expressing reduced X11alpha suggest a normal suppressor role for X11alpha on CNS Abeta/amyloid deposition.
Publication types
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Research Support, N.I.H., Extramural
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Research Support, U.S. Gov't, Non-P.H.S.
MeSH terms
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Adaptor Proteins, Signal Transducing / classification
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Adaptor Proteins, Signal Transducing / deficiency*
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Adaptor Proteins, Signal Transducing / genetics
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Alzheimer Disease / genetics*
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Alzheimer Disease / metabolism*
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Alzheimer Disease / pathology
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Amyloid beta-Peptides / metabolism*
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Amyloid beta-Protein Precursor / genetics
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Animals
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Brain / metabolism*
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Brain / pathology
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Disease Models, Animal
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Enzyme-Linked Immunosorbent Assay / methods
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Gene Expression Regulation / genetics
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Humans
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Membrane Proteins / classification
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Membrane Proteins / deficiency*
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Membrane Proteins / genetics
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Mice
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Mice, Inbred C57BL
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Mice, Transgenic
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Mutation / genetics
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Peptide Fragments / metabolism
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Presenilin-1 / genetics
Substances
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Adaptor Proteins, Signal Transducing
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Amyloid beta-Peptides
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Amyloid beta-Protein Precursor
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Apba1 protein, rat
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Membrane Proteins
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PSEN1 protein, human
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Peptide Fragments
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Presenilin-1
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amyloid beta-protein (1-40)
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amyloid beta-protein (1-42)