Mixed pathology as a rule, not exception: Time to reconsider disease nosology

Yaping Chu, Warren D. Hirst, Jeffrey H. Kordower

Research output: Contribution to journalReview articlepeer-review

Abstract

Parkinson's disease is a progressive neurodegenerative disorder that is associated with motor and nonmotor symptoms. Accumulation of misfolded α-synuclein is considered a key pathological feature during disease initiation and progression. While clearly deemed a synucleinopathy, the development of amyloid-β plaques, tau-containing neurofibrillary tangles, and even TDP-43 protein inclusions occur within the nigrostriatal system and in other brain regions. In addition, inflammatory responses, manifested by glial reactivity, T-cell infiltration, and increased expression of inflammatory cytokines, plus other toxic mediators derived from activated glial cells, are currently recognized as prominent drivers of Parkinson's disease pathology. However, copathologies have increasingly been recognized as the rule (>90%) and not the exception, with Parkinson's disease cases on average exhibiting three different copathologies. While microinfarcts, atherosclerosis, arteriolosclerosis, and cerebral amyloid angiopathy may have an impact on disease progression, α-synuclein, amyloid-β, and TDP-43 pathology do not seem to contribute to progression.

Original languageEnglish (US)
Pages (from-to)57-71
Number of pages15
JournalHandbook of Clinical Neurology
Volume192
DOIs
StatePublished - 2023

Keywords

  • Alpha-synuclein
  • Amyloid
  • Inflammation
  • Parkinson disease
  • Proteinopathy
  • Tau

ASJC Scopus subject areas

  • Neurology
  • Clinical Neurology

Fingerprint

Dive into the research topics of 'Mixed pathology as a rule, not exception: Time to reconsider disease nosology'. Together they form a unique fingerprint.

Cite this