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The Alzheimer amyloid precursor is associated with the detergent- insoluble cytoskeleton

LM Refolo, IS Wittenberg, VL Friedrich Jr and NK Robakis
Journal of Neuroscience 1 December 1991, 11 (12) 3888-3897; DOI: https://doi.org/10.1523/JNEUROSCI.11-12-03888.1991
LM Refolo
Department of Psychiatry, Mount Sinai School of Medicine, New York, New York 10029.
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IS Wittenberg
Department of Psychiatry, Mount Sinai School of Medicine, New York, New York 10029.
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VL Friedrich Jr
Department of Psychiatry, Mount Sinai School of Medicine, New York, New York 10029.
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NK Robakis
Department of Psychiatry, Mount Sinai School of Medicine, New York, New York 10029.
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Abstract

The amyloid beta-protein (A beta P), the main component of neuritic plaques in Alzheimer's disease (AD), is derived by unknown mechanisms from a family of amyloid precursor proteins (APPs). Using a detergent extraction procedure, we have found that in brain and in neural cell lines, 50-90% of APP is bound to detergent-insoluble cytoskeleton. Labeling experiments performed in a C6 glioma cell line indicated that both cell surface and intracellular APPs are associated with the cytoskeleton. This association requires intact microtubules and is modulated by protein phosphorylation and by cell density. These findings suggest that the function of cellular APP, presently unknown, involves the cytoskeleton and particularly microtubules. The dynamic nature of the binding and its dependence on microtubules and protein phosphorylation suggest it as a possible target in AD, where abnormal cytoskeletal structures and protein phosphorylation have been reported. Altered cytoskeletal binding of APP might lead to its aberrant proteolysis and generation of the A beta P.

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The Journal of Neuroscience: 11 (12)
Journal of Neuroscience
Vol. 11, Issue 12
1 Dec 1991
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The Alzheimer amyloid precursor is associated with the detergent- insoluble cytoskeleton
LM Refolo, IS Wittenberg, VL Friedrich Jr, NK Robakis
Journal of Neuroscience 1 December 1991, 11 (12) 3888-3897; DOI: 10.1523/JNEUROSCI.11-12-03888.1991

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The Alzheimer amyloid precursor is associated with the detergent- insoluble cytoskeleton
LM Refolo, IS Wittenberg, VL Friedrich Jr, NK Robakis
Journal of Neuroscience 1 December 1991, 11 (12) 3888-3897; DOI: 10.1523/JNEUROSCI.11-12-03888.1991
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