Glucocerebrosidase mutations are an important risk factor for Lewy body disorders.
The synucleinopathies are neurodegenerative disorders defined by inclusions composed of aberrantly fibrillized alpha-synuclein, but factors contributing to this process remain largely unknown. The authors examined the glucocerebrosidase gene in 75 autopsy specimens with different synucleinopathies and identified mutations in 23% of cases of dementia with Lewy bodies, expanding on previous findings in subjects with Parkinson disease. Mutations in this lysosomal protein may interfere with the clearance or promote aggregation of alpha-synuclein.
Goker-Alpan
O
O
Section on Molecular Neurogenetics, Medical Genetics Branch, National Human Genome Research Institute, NIH, Bethesda, MD 20892-3708, USA.
Giasson
B I
BI
Eblan
M J
MJ
Nguyen
J
J
Hurtig
H I
HI
Lee
V M-Y
VM
Trojanowski
J Q
JQ
Sidransky
E
E
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D001216:Asparagine / Q000235:genetics; D001344:Autopsy; D001921:Brain / Q000473:pathology; D004252:DNA Mutational Analysis / Q000379:methods; D005260:Female; D005962:Glucosylceramidase / Q000235:genetics*; D006801:Humans; D007532:Isoleucine / Q000235:genetics; D020961:Lewy Body Disease / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D008297:Male; D008875:Middle Aged; D009154:Mutation; D010300:Parkinson Disease / Q000235:genetics / Q000473:pathology; D012307:Risk Factors; D051843:Synucleins / Q000378:metabolism; D013912:Threonine / Q000235:genetics
D051843:Synucleins; D007532:Isoleucine; D013912:Threonine; D001216:Asparagine; D005962:Glucosylceramidase