title: First appraisal of brain pathology owing to A30P mutant alpha-synuclein.
abstract: Familial Parkinson disease (PD) due to the A30P mutation in the SNCA gene encoding alpha-synuclein is clinically associated with PD symptoms. In this first pathoanatomical study of the brain of an A30P mutation carrier, we observed neuronal loss in the substantia nigra, locus coeruleus, and dorsal motor vagal nucleus, as well as widespread occurrence of alpha-synuclein immunopositive Lewy bodies, Lewy neurites, and glial aggregates. Alpha-synuclein aggregates ultrastructurally resembled Lewy bodies, and biochemical analyses disclosed a significant load of insoluble alpha-synuclein, indicating neuropathological similarities between A30P disease patients and idiopathic PD, with a more severe neuropathology in A30P carriers.
authors.affiliation: Institute of Clinical Neuroanatomy, Dr Senckenberg Anatomy, Goethe University, Frankfurt am Main, Germany.
authors.forename: Kay
authors.initials: K
authors.lastname: Seidel
authors.forename: Ludger
authors.initials: L
authors.lastname: Schöls
authors.forename: Silke
authors.initials: S
authors.lastname: Nuber
authors.forename: Elisabeth
authors.initials: E
authors.lastname: Petrasch-Parwez
authors.forename: Kristin
authors.initials: K
authors.lastname: Gierga
authors.forename: Zbigniew
authors.initials: Z
authors.lastname: Wszolek
authors.forename: Dennis
authors.initials: D
authors.lastname: Dickson
authors.forename: Wei P
authors.initials: WP
authors.lastname: Gai
authors.forename: Antje
authors.initials: A
authors.lastname: Bornemann
authors.forename: Olaf
authors.initials: O
authors.lastname: Riess
authors.forename: Abdelhaq
authors.initials: A
authors.lastname: Rami
authors.forename: Wilfried F A
authors.initials: WF
authors.lastname: Den Dunnen
authors.forename: Thomas
authors.initials: T
authors.lastname: Deller
authors.forename: Udo
authors.initials: U
authors.lastname: Rüb
authors.forename: Rejko
authors.initials: R
authors.lastname: Krüger
mesh_terms: D000368:Aged; D000409:Alanine / Q000235:genetics; D001921:Brain / Q000473:pathology* / Q000648:ultrastructure; D001927:Brain Diseases / Q000235:genetics* / Q000473:pathology*; D005192:Family Health; D005904:Glial Fibrillary Acidic Protein / Q000378:metabolism; D006801:Humans; D002479:Inclusion Bodies / Q000473:pathology; D008297:Male; D009154:Mutation / Q000235:genetics*; D011392:Proline / Q000235:genetics; D051844:alpha-Synuclein / Q000235:genetics*
chemical_list: D005904:Glial Fibrillary Acidic Protein; D051844:alpha-Synuclein; D011392:Proline; D000409:Alanine