Parkinsonism, Lrrk2 G2019S, and tau neuropathology.
Lrrk2 G2019S is predominantly associated with alpha-synuclein-immunopositive Lewy body pathology. We have identified Family SK where Lrrk2 G2019S segregates with slowly progressive parkinsonism and the affected proband has tau-immunopositive neurofibrillary tangle pathology. Thus alpha-synucleinopathy and tauopathy, the predominant pathologies associated with parkinsonism, may be alternate outcomes of the same underlying genetic cause. Intriguingly, we observe no evidence of a direct interaction between either the tau or alpha-synuclein protein with Lrrk2.
Rajput
A
A
Division of Neurology, University of Saskatchewan and Saskatoon Health Region, Saskatoon, Saskatchewan, Canada.
Dickson
D W
DW
Robinson
C A
CA
Ross
O A
OA
Dächsel
J C
JC
Lincoln
S J
SJ
Cobb
S A
SA
Rajput
M L
ML
Farrer
M J
MJ
D000368:Aged; D001921:Brain / Q000378:metabolism / Q000473:pathology; D002460:Cell Line; D004185:Disability Evaluation; D018450:Disease Progression; D005260:Female; D005998:Glycine; D006801:Humans; D007150:Immunohistochemistry; D000071158:Leucine-Rich Repeat Serine-Threonine Protein Kinase-2; D008297:Male; D008875:Middle Aged; D009154:Mutation; D016874:Neurofibrillary Tangles / Q000378:metabolism* / Q000473:pathology; D020734:Parkinsonian Disorders / Q000235:genetics* / Q000473:pathology* / Q000503:physiopathology; D010375:Pedigree; D017346:Protein Serine-Threonine Kinases / Q000235:genetics*; D012694:Serine; D051844:alpha-Synuclein / Q000378:metabolism; D016875:tau Proteins / Q000378:metabolism*
D051844:alpha-Synuclein; D016875:tau Proteins; D012694:Serine; C495280:LRRK2 protein, human; D000071158:Leucine-Rich Repeat Serine-Threonine Protein Kinase-2; D017346:Protein Serine-Threonine Kinases; D005998:Glycine