First appraisal of brain pathology owing to A30P mutant alpha-synuclein.
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.
Seidel
Kay
K
Institute of Clinical Neuroanatomy, Dr Senckenberg Anatomy, Goethe University, Frankfurt am Main, Germany.
Schöls
Ludger
L
Nuber
Silke
S
Petrasch-Parwez
Elisabeth
E
Gierga
Kristin
K
Wszolek
Zbigniew
Z
Dickson
Dennis
D
Gai
Wei P
WP
Bornemann
Antje
A
Riess
Olaf
O
Rami
Abdelhaq
A
Den Dunnen
Wilfried F A
WF
Deller
Thomas
T
Rüb
Udo
U
Krüger
Rejko
R
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*
D005904:Glial Fibrillary Acidic Protein; D051844:alpha-Synuclein; D011392:Proline; D000409:Alanine