Selective neuronal vulnerability in Parkinson disease

D. James Surmeier, José A. Obeso, Glenda M. Halliday

Research output: Contribution to journalReview articlepeer-review

615 Scopus citations


Intracellular α-synuclein (α-syn)-rich protein aggregates called Lewy pathology (LP) and neuronal death are commonly found in the brains of patients with clinical Parkinson disease (cPD). It is widely believed that LP appears early in the disease and spreads in synaptically coupled brain networks, driving neuronal dysfunction and death. However, post-mortem analysis of human brains and connectome-mapping studies show that the pattern of LP in cPD is not consistent with this simple model, arguing that, if LP propagates in cPD, it must be gated by cell-or region-Autonomous mechanisms. Moreover, the correlation between LP and neuronal death is weak. In this Review, we briefly discuss the evidence for and against the spreading LP model, as well as evidence that cell-Autonomous factors govern both α-syn pathology and neuronal death.

Original languageEnglish (US)
Pages (from-to)101-113
Number of pages13
JournalNature Reviews Neuroscience
Issue number2
StatePublished - Feb 1 2017

ASJC Scopus subject areas

  • General Neuroscience


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