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01-05-2011 | Original paper

Granular expression of prolyl-peptidyl isomerase PIN1 is a constant and specific feature of Alzheimer’s disease pathology and is independent of tau, Aβ and TDP-43 pathology

Authors: Ayoub Dakson, Osamu Yokota, Margaret Esiri, Eileen H. Bigio, Michael Horan, Neil Pendleton, Anna Richardson, David Neary, Julie S. Snowden, Andrew Robinson, Yvonne S. Davidson, David M. A. Mann

Published in: Acta Neuropathologica | Issue 5/2011

Abstract

Alzheimer’s disease (AD) manifests with progressive memory loss and decline of spatial awareness and motor skills. Neurofibrillary tangles (NFTs) represent one of the pathological hallmarks of AD. Previous studies suggest that the enzyme prolyl-peptidyl cis–trans isomerase PIN1 [protein interacting with NIMA (never in mitosis A)-1] recognizes hyperphosphorylated tau (in NFTs) and facilitates its dephosphorylation, thereby recovering its function. This study aims to determine the frequency, severity and distribution of PIN1 immunoreactivity and its relationship to NFTs and other neuropathological markers of neurodegeneration such as amyloid-β (Aβ) plaques and transcription-responsive DNA-binding protein of M _r 43 kDa (TDP-43). Immunohistochemical analysis of 194 patients (46 with AD, 43 with Parkinson’s disease/dementia with Lewy bodies, 12 with progressive supranuclear palsy/corticobasal degeneration, 36 with frontotemporal lobar degeneration, 21 with motor neuron disease and 34 non-demented (ND) individuals) revealed an increased frequency and severity of PIN1 immunoreactive inclusions in AD as compared to all diagnostic groups (P < 0.001). The hippocampal and cortical distribution of PIN1 granules was distinct from that of NFTs, Aβ and TDP-43 pathologies, though the frequency of neurons with PIN1 immunoreactivity increased with increasing NFT pathology. There was a progressive increase in PIN1 changes in ND individuals as the degree of AD-type pathological changes increased. Present findings indicate that PIN1 changes are a constant feature of AD pathology and could serve as a biomarker of the onset or spread of AD neuropathology independent of tau or Aβ.

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Title: Granular expression of prolyl-peptidyl isomerase PIN1 is a constant and specific feature of Alzheimer’s disease pathology and is independent of tau, Aβ and TDP-43 pathology
Authors: Ayoub Dakson
Osamu Yokota
Margaret Esiri
Eileen H. Bigio
Michael Horan
Neil Pendleton
Anna Richardson
David Neary
Julie S. Snowden
Andrew Robinson
Yvonne S. Davidson
David M. A. Mann
Publication date: 01-05-2011
Publisher: Springer-Verlag
Published in: Acta Neuropathologica / Issue 5/2011
Print ISSN: 0001-6322
Electronic ISSN: 1432-0533
DOI: https://doi.org/10.1007/s00401-011-0798-y

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Granular expression of prolyl-peptidyl isomerase PIN1 is a constant and specific feature of Alzheimer’s disease pathology and is independent of tau, Aβ and TDP-43 pathology

Abstract

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