Ferreira DG, Temido-Ferreira M, Miranda HV, Batalha VL, Coelho JE, Szegö ÉM, Marques-Morgado I, Vaz SH, Rhee JS, Schmitz M, Zerr I, Lopes LV, Outeiro TF. α-synuclein interacts with PrP(C) to induce cognitive impairment through mGluR5 and NMDAR2B. Nat Neurosci. 2017 Nov;20(11):1569-1579. Epub 2017 Sep 25 PubMed.
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University Medical Center Goettingen
PD is no longer viewed simply as a movement disorder. Numerous non-motor features, including hyposmia, REM sleep disturbances, autonomic dysfunction, and impaired cognitive function, are now known to be present, and to often appear sequentially as disease progresses. The precise molecular determinants of disease progression are still unclear, but it is possible that the spreading of α-synuclein pathology from the periphery to the brain, or from the brain to the periphery, may be related to the progressive nature of the disease.
Diagnosing PD, or other neurodegenerative disorders, is rather challenging, as we still lack established biomarkers that allow us to detect the initial signs of the disease, prior to the overt onset of the typical symptoms. Therefore, studies like this one now published in JAMA are exciting in that they suggest that poor cognitive function might be used as an early indicator of the risk for PD. The study suffers from some limitations, as carefully explained in the accompanying editorial, but still has numerous implications that are worth pursuing in future studies. In particular, it focuses our attention on cognitive function as an important feature in PD. Interestingly, this links nicely with the findings of our study published on the same day (Ferreira et al., 2017), in which we detail the effects of α-synuclein in the hippocampus, via an interaction with the prion protein (PrP). Our study does not solve all questions related to cognitive impairment in PD, but suggests some novel targets that can be explored to treat an important and debilitating feature in PD.
In conclusion, these new studies suggest cognitive impairment may be an indicator of the risk for PD and also a symptom than can be targeted therapeutically. These are exciting times for research, but especially for PD patients and their families.
References:
Ferreira DG, Temido-Ferreira M, Miranda HV, Batalha VL, Coelho JE, Szegö ÉM, Marques-Morgado I, Vaz SH, Rhee JS, Schmitz M, Zerr I, Lopes LV, Outeiro TF. α-synuclein interacts with PrP(C) to induce cognitive impairment through mGluR5 and NMDAR2B. Nat Neurosci. 2017 Nov;20(11):1569-1579. Epub 2017 Sep 25 PubMed.
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