Clathrin adaptor CALM/PICALM is associated with neurofibrillary tangles and is cleaved in Alzheimer's brains.

Abstract:

:PICALM, a clathrin adaptor protein, plays important roles in clathrin-mediated endocytosis in all cell types. Recently, genome-wide association studies identified single nucleotide polymorphisms in PICALM gene as genetic risk factors for late-onset Alzheimer disease (LOAD). We analysed by western blotting with several anti-PICALM antibodies the pattern of expression of PICALM in human brain extracts. We found that PICALM was abnormally cleaved in AD samples and that the level of the uncleaved 65-75 kDa full-length PICALM species was significantly decreased in AD brains. Cleavage of human PICALM after activation of endogenous calpain or caspase was demonstrated in vitro. Immunohistochemistry revealed that PICALM was associated in situ with neurofibrillary tangles, co-localising with conformationally abnormal and hyperphosphorylated tau in LOAD, familial AD and Down syndrome cases. PHF-tau proteins co-immunoprecipitated with PICALM. PICALM was highly expressed in microglia in LOAD. These observations suggest that PICALM is associated with the development of AD tau pathology. PICALM cleavage could contribute to endocytic dysfunction in AD.

journal_name

Acta Neuropathol

journal_title

Acta neuropathologica

authors

Ando K,Brion JP,Stygelbout V,Suain V,Authelet M,Dedecker R,Chanut A,Lacor P,Lavaur J,Sazdovitch V,Rogaeva E,Potier MC,Duyckaerts C

doi

10.1007/s00401-013-1111-z

subject

Has Abstract

pub_date

2013-06-01 00:00:00

pages

861-78

issue

6

eissn

0001-6322

issn

1432-0533

journal_volume

125

pub_type

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