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

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


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.

Publication types

  • Research Support, N.I.H., Extramural
  • Review

MeSH terms

  • Alzheimer Disease / pathology*
  • Alzheimer Disease / physiopathology
  • Amyloid beta-Peptides / physiology*
  • Brain / pathology
  • Brain / physiology
  • Humans
  • Neurons / pathology
  • Neurons / physiology
  • Parkinson Disease / pathology*
  • Parkinson Disease / physiopathology
  • alpha-Synuclein / physiology*
  • tau Proteins / physiology*


  • Amyloid beta-Peptides
  • SNCA protein, human
  • alpha-Synuclein
  • tau Proteins