Comparison of Kindreds with Parkinsonism and α-Synuclein Genomic Multiplications

Matt Farrer, Jennifer Kachergus, Lysia Forno, Sarah Lincoln, Deng Shun Wang, Mary Hulihan, Demetrius Maraganore, Katrina Gwinn-Hardy, Zbigniew Wszolek, Dennis Dickson, J. William Langston

Research output: Contribution to journalArticle

528 Scopus citations

Abstract

Genomic triplication of the α-synuclein gene recently has been associated with familial Parkinson's disease in the Spellman-Muenter kindred. Here, we present an independent family, of Swedish-American descent, with hereditary early-onset parkinsonism with dementia due to α-synuclein triplication. Brain tissue available from affected individuals in both kindreds provided the opportunity to compare their clinical, pathological, and biochemical phenotypes. Of note, studies of brain mRNA and soluble protein levels demonstrate a doubling of α-synuclein expression, consistent with molecular genetic data. Pathologically, cornu ammonis 2/3 hippocampal neuronal loss appears to be a defining feature of this form of inherited parkinsonism. The profound implications of α-synuclein overexpression for idiopathic synucleinopathies are discussed.

Original languageEnglish (US)
Pages (from-to)174-179
Number of pages6
JournalAnnals of neurology
Volume55
Issue number2
DOIs
StatePublished - Feb 2004

ASJC Scopus subject areas

  • Neurology
  • Clinical Neurology

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