Parkinson's disease dementia: convergence of α-synuclein, tau and amyloid-β pathologies

Dementia is increasingly being recognized in cases of Parkinson's disease (PD); such cases are termed PD dementia (PDD). The spread of fibrillar alpha-synuclein (alpha-syn) pathology from the brainstem to limbic and neocortical structures seems to be the strongest neuropathological correlate of emerging dementia in PD. In addition, up to 50% of patients with PDD also develop sufficient numbers of amyloid-beta plaques and tau-containing neurofibrillary tangles for a secondary diagnosis of Alzheimer's disease, and these pathologies may act synergistically with alpha-syn pathology to confer a worse prognosis. An understanding of the relationships between these three distinct pathologies and their resultant clinical phenotypes is crucial for the development of effective disease-modifying treatments for PD and PDD.