. A meta-analysis of genome-wide association studies identifies 17 new Parkinson's disease risk loci. Nat Genet. 2017 Sep 11; PubMed.


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  1. The connection between lysosome dysfunction and Parkinson’s disease is now clear. These papers—as well as one this week by Schapira in Brain and another due out soon from Shulman, Heutink, and the IPDGC—show clearly that lysosome dysfunction, going beyond GBA loss, is key to Parkinson’s pathogenesis. This is indeed an exciting insight.

    It is also the case that most pure frontotemporal dementias are caused by different variants in the endosomal/lysosome system. In some sense, one can think of these diseases as formes frustes of lysosome storage diseases.  

    Less easy to understand is the idea of a “special relationship” between lysosomal storage diseases and dopamine neurons, since we now know there is nothing special about DA neurons in PD. Braaks’ staging and other work shows that the substantia nigra neurons are but one type of neuron hit by the PD process. They are not the first, and the process is by no means selective.


    . The L444P Gba1 mutation enhances alpha-synuclein induced loss of nigral dopaminergic neurons in mice. Brain, 21 Sept. 2017

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