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.
No takes yet. Share an insight, caveat, or question.
Compta et al. (2013) studied this question.
Synapse has enriched 5 closely related papers on similar clinical questions. Consider them for comparative context:
More from Neurodegenerative Diseases