Together, these findings place LRRK2 together with LRP1 as contributing to tauopathy pathogenesis, and suggest that small molecule inhibition of LRRK2, or reduction in LRRK2 protein levels, may have roles in slowing disease progression in neurodegenerative diseases involving spread of tau aggregation, including Alzheimer’s disease, as well as PD progression mediated by alpha-synuclein. Here, LRRK2 is linked to early-onset autosomal dominant Alzheimer disease.