Axon pathology in Parkinson's disease and Lewy body dementia hippocampus contains α-, β-, and γ-synuclein

James E. Galvin, Kunihiro Uryu, Virginia M.Y. Lee, John Q. Trojanowski

Research output: Contribution to journalArticlepeer-review

344 Scopus citations

Abstract

Pathogenic α-synuclein (αS) gene mutations occur in rare familial Parkinson's disease (PD) kindreds, and wild-type αS is a major component of Lewy bodies (LBs) in sporadic PD, dementia with LBs (DLB), and the LB variant of Alzheimer's disease, but β-synuclein (βS) and γ-synuclein (γ5) have not yet been implicated in neurological disorders. Here we show that in PD and DLB, but not normal brains, antibodies to αS and βS reveal novel presynaptic axon terminal pathology in the hippocampal dentate, hilar, and CA2/3 regions, whereas antibodies to γS detect previously unrecognized axonal spheroid-like lesions in the hippocampal dentate molecular layer. The aggregation of other synaptic proteins and synaptic vesicle-like structures in the αS- and βS-labeled hilar dystrophic neurites suggests that synaptic dysfunction may result from these lesions. Our findings broaden the concept of neurodegenerative "synucleinopathies" by implicating βS and γS, in addition to αS, in the onset/progression of PD and DLB.

Original languageEnglish (US)
Pages (from-to)13450-13455
Number of pages6
JournalProceedings of the National Academy of Sciences of the United States of America
Volume96
Issue number23
DOIs
StatePublished - Nov 9 1999
Externally publishedYes

Keywords

  • Mossy fibers
  • Perforant pathway

ASJC Scopus subject areas

  • General

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