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Open Access 01-04-2008 | Original Paper

Applicability of current staging/categorization of α-synuclein pathology and their clinical relevance

Authors: Laura Parkkinen, Tuula Pirttilä, Irina Alafuzoff

Published in: Acta Neuropathologica | Issue 4/2008

Abstract

In Parkinson’s disease (PD) and dementia with Lewy bodies (DLB) α-synuclein (αS) pathology is seen that displays a predictable topographic distribution. There are two staging/categorization systems, i.e. Braak’s and McKeith’s, currently in use for the assessment of αS pathology. The aim of these diagnostic strategies in pathology is, in addition to assess the stage/severity of pathology, to assess the probabilities of the related clinical symptomatology i.e. dementia and extrapyramidal symptoms (EPS). Herein, we assessed the applicability of these two staging/categorization systems and the frequency of dementia and EPS in a cohort of 226 αS-positive-subjects. These subject were selected from a large autopsy sample (n = 1,720), irrespective of the clinical presentation, based on the detection of αS-immunoreactivity (IR) in one of the most vulnerable nuclei; in the dorsal motor nucleus of vagus, substantia nigra and basal forebrain. The frequency of αS-IR lesions in this large cohort was 14% (248 out of 1,720). If applicable, each of the 226 subjects with all required material available was assigned a neuropathological stage/category of PD/DLB and finally the neuropathological data was analyzed in relation to dementia and EPS. 83% of subjects showed a distribution pattern of αS-IR that was compatible with the current staging/categorization systems. Around 55% of subjects with widespread αS pathology (Braak’s PD stages 5–6) lacked clinical signs of dementia or EPS. Similarly, in respect to those subjects that fulfilled the McKeith criteria for diffuse neocortical category and displaying only mild concomitant Alzheimer’s disease-related pathology, only 48% were demented and 54% displayed EPS. It is noteworthy that some subjects (17%) deviated from the suggested caudo-rostral propagation suggesting alternative routes of progression, perhaps due to concomitant diseases and genetic predisposition. In conclusion, our results do indeed confirm that current staging/categorization systems can readily be applied to most of the subjects with αS pathology. However, finding that around half of the subjects with abundant αS pathology remain neurologically intact is intriguing and raises the question whether we do assess the actual disease process.

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Title: Applicability of current staging/categorization of α-synuclein pathology and their clinical relevance
Authors: Laura Parkkinen
Tuula Pirttilä
Irina Alafuzoff
Publication date: 01-04-2008
Publisher: Springer-Verlag
Published in: Acta Neuropathologica / Issue 4/2008
Print ISSN: 0001-6322
Electronic ISSN: 1432-0533
DOI: https://doi.org/10.1007/s00401-008-0346-6

At a glance: The STEP trials

Springer Medicine

Applicability of current staging/categorization of α-synuclein pathology and their clinical relevance

Abstract

At a glance: The STEP trials

Springer Medicine

Abstract

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