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. 2014;13(2-3):154-6.
doi: 10.1159/000354670. Epub 2013 Sep 11.

The significance of α-synuclein, amyloid-β and tau pathologies in Parkinson's disease progression and related dementia

Yaroslau Compta  1 , Laura Parkkinen, Peter Kempster, Mariana Selikhova, Tammaryn Lashley, Janice L Holton, Andrew J Lees, Tamas Revesz
Affiliations

The significance of α-synuclein, amyloid-β and tau pathologies in Parkinson's disease progression and related dementia

Yaroslau Compta et al. Neurodegener Dis. 2014.

Abstract

Background: Dementia is one of the milestones of advanced Parkinson's disease (PD), with its neuropathological substrate still being a matter of debate, particularly regarding its potential mechanistic implications.

Objective: The aim of this study was to review the relative importance of Lewy-related α-synuclein and Alzheimer's tau and amyloid-β (Aβ) pathologies in disease progression and dementia in PD.

Methods: We reviewed studies conducted at the Queen Square Brain Bank, Institute of Neurology, University College London, using large PD cohorts.

Results: Cortical Lewy- and Alzheimer-type pathologies are associated with milestones of poorer prognosis and with non-tremor predominance, which have been, in turn, linked to dementia. The combination of these pathologies is the most robust neuropathological substrate of PD-related dementia, with cortical Aβ burden determining a faster progression to dementia.

Conclusion: The shared relevance of these pathologies in PD progression and dementia is in line with experimental data suggesting synergism between α-synuclein, tau and Aβ and with studies testing these proteins as disease biomarkers, hence favouring the eventual testing of therapeutic strategies targeting these proteins in PD.

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