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First appraisal of brain pathology owing to A30P mutant alpha‐synuclein
Author(s) -
Seidel Kay,
Schöls Ludger,
Nuber Silke,
PetraschParwez Elisabeth,
Gierga Kristin,
Wszolek Zbigniew,
Dickson Dennis,
Gai Wei P.,
Bornemann Antje,
Riess Olaf,
Rami Abdelhaq,
Den Dunnen Wilfried F. A.,
Deller Thomas,
Rüb Udo,
Krüger Rejko
Publication year - 2010
Publication title -
annals of neurology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 4.764
H-Index - 296
eISSN - 1531-8249
pISSN - 0364-5134
DOI - 10.1002/ana.21966
Subject(s) - locus coeruleus , alpha synuclein , neuropathology , lewy body , substantia nigra , pathology , neuroscience , synuclein , parkinson's disease , degenerative disease , chemistry , medicine , biology , nucleus , central nervous system disease , disease
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. ANN NEUROL 2010;67:684–689