Parkinsonism, Lrrk2 G2019S, and tau neuropathology

Lrrk2 G2019S is predominantly associated with α-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 α-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 α-synuclein protein with Lrrk2.