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Nat Rev Neurosci. 2013 Sep;14(9):626-36. doi: 10.1038/nrn3549. Epub 2013 Jul 31.

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

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Center for Neurodegenerative Disease Research, Department of Pathology and Laboratory Medicine, Alzheimer's Disease Core Center, Institute on Aging, University of Pennsylvania Perelman School of Medicine, HUP, Maloney 3rd Floor, 36th and Spruce Streets, Philadelphia, Pennsylvania 19104-4283, USA.


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.

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