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

L. M. Refolo, I. S. Wittenberg, V. L. Friedrich, N. K. Robakis

Research output: Contribution to journalArticlepeer-review

76 Scopus citations

Abstract

The amyloid β-protein (AβP), 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 AβP.

Original languageEnglish
Pages (from-to)3888-3897
Number of pages10
JournalJournal of Neuroscience
Volume11
Issue number12
DOIs
StatePublished - 1991

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