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

Many cases of Parkinson's disease (PD) are characterized by not only deficits in movement but also cognitive dysfunction, which can develop into dementia. Here, Irwinet al. review the complex connections between the neuropathological aetiologies that underlie the cognitive deficits associated with PD. Dementia is increasingly being recognized in cases of Parkinson's disease (PD); such cases are termed PD dementia (PDD). The spread of fibrillar α-synuclein (α-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-β plaques and tau-containing neurofibrillary tangles for a secondary diagnosis of Alzheimer's disease, and these pathologies may act synergistically with α-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.