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

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.

• Authors: Yaroslau Compta, Laura Parkkinen, Peter Kempster, Mariana Selikhova, Tammaryn Lashley, Janice L Holton, Andrew J Lees, Tamas Revesz
• Journal: Neuro-degenerative diseases (Neurodegener Dis) Vol. 13 Issue 2-3 Pg. 154-6 ( 2014) ISSN: 1660-2862 [Electronic] Switzerland
• PMID: 24028925 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Amyloid beta-Peptides
• alpha-Synuclein
• tau Proteins

Topics

• Amyloid beta-Peptides (metabolism)
• Brain (metabolism, pathology)
• Dementia (etiology, metabolism, pathology)
• Disease Progression
• Humans
• Parkinson Disease (complications, metabolism, pathology)
• Retrospective Studies
• alpha-Synuclein (metabolism)
• tau Proteins (metabolism)