Lrrk2 and Lewy body disease.
OBJECTIVE
The Lrrk2 kinase domain G2019S substitution is the most common genetic basis of familial and sporadic parkinsonism. Patients harboring the G2019S substitution usually present with clinical Parkinson's disease.


METHODS
Herein, we report that the most common neuropathology of G2019S-associated Parkinson's disease is Lewy body disease.


RESULTS
Lrrk2 G2019S was observed in approximately 2% (n = 8) of our Parkinson's disease/Lewy body disease cases (n = 405). The mutation was also found in one control subject and one Alzheimer's disease patient, reflecting reduced penetrance.


CONCLUSIONS
Therapeutic strategies targeted at modulating Lrrk2 kinase activity may be important to treat patients with genetically defined familial or typical sporadic Parkinson's disease.
Ross
Owen A
OA
Department of Neuroscience, Mayo Clinic College of Medicine, Jacksonville, FL 32224, USA.
Toft
Mathias
M
Whittle
Andrew J
AJ
Johnson
Joseph L
JL
Papapetropoulos
Spiridon
S
Mash
Deborah C
DC
Litvan
Irene
I
Gordon
Mark F
MF
Wszolek
Zbigniew K
ZK
Farrer
Matthew J
MJ
Dickson
Dennis W
DW
D000368:Aged; D000369:Aged, 80 and over; D001933:Brain Stem / Q000378:metabolism / Q000473:pathology; D004252:DNA Mutational Analysis / Q000379:methods; D005260:Female; D005998:Glycine / Q000235:genetics; D006801:Humans; D000071158:Leucine-Rich Repeat Serine-Threonine Protein Kinase-2; D020961:Lewy Body Disease / Q000235:genetics*; D008297:Male; D008958:Models, Molecular; D009154:Mutation; D017346:Protein Serine-Threonine Kinases / Q000235:genetics*; D011506:Proteins / Q000235:genetics
D011506:Proteins; C475853:serin-rich spermatogenic protein 1, rat; C495280:LRRK2 protein, human; D000071158:Leucine-Rich Repeat Serine-Threonine Protein Kinase-2; D017346:Protein Serine-Threonine Kinases; D005998:Glycine