P38 MAP kinase is activated at early stages in Alzheimer's disease brain.

Abstract:

:The regional, cellular, and subcellular localization of phosphorylated p38 MAPK (pp38) was examined by immunocytochemistry, immuofluorescent multiple labeling, and immunoblotting of extracts as well as immunoprecipitates of human postmortem tissue from control and Alzheimer's disease (AD) cases at different Braak stages. "Early AD" cases (Braak stages IV-V) and a subset of Braak stage VI cases have high levels of pp38 immunoreactivity, with the most dense immunoreactivity located in CA2 and subiculum followed by CA1 in the hippocampus. On the contrary, very little pp38 was detected in age-matched controls (Braak stages 0-II). More importantly, as revealed by various multiple labeling experiments, pp38 immunoreactivity is mainly located in neurons bearing early neurofibrillary pathology, but not in typically fibrillar tangles that are densely stained by thioflavin-S. Most pp38-positive neurons only contain a small amount of phospho-tau. Additionally, pp38 immunoreactivity was not associated with senile plaques. At the subcellular level, pp38-immunoreactive granules are usually larger than the granules stained with the lysosomal marker cathepsin D. Immunoblotting with different extraction buffers and immunoprecipitation indicate that pp38 does not or only loosely binds to phospho-tau. Taken together, this study demonstrates that p38 MAPK is activated at early stages of neurofibrillary degeneration in AD hippocampus. The p38 activation may also be linked to neurodegeneration through mechanisms other than neurofibrillary tangle formation.

journal_name

Exp Neurol

journal_title

Experimental neurology

authors

Sun A,Liu M,Nguyen XV,Bing G

doi

10.1016/s0014-4886(03)00180-8

keywords:

subject

Has Abstract

pub_date

2003-10-01 00:00:00

pages

394-405

issue

2

eissn

0014-4886

issn

1090-2430

pii

S0014488603001808

journal_volume

183

pub_type

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