PSOM Center on Mechanisms Underlying Cognitive Heterogeneity in Synucleinopathy

Mission

The overall goal of this Penn PO1 Center on “Mechanisms underlying heterogeneity of cognitive outcome in synucleinopathy” is to understand why the same underlying core pathology – inclusions of alpha-synuclein (aSyn) – varies so widely in the pace and pattern of spread within the brain, resulting in dramatically divergent clinical trajectories. The Lewy body disorders (LBD) – namely, dementia with Lewy bodies (DLB), Parkinson’s disease (PD), Parkinson’s disease with dementia (PDD), and, to some extent, Alzheimer’s Disease with Lewy bodies (LBD+AD) – share the central feature of neuronal aSyn inclusions. However, LBD patients manifest very differently from one another, with differences in cognition playing a vital role with respect to patient quality of life and burden to the healthcare system. Indeed, individuals with DLB manifest with cognitive symptoms, while the point prevalence of dementia in PD in the US is estimated at 30%. That said, >80% of PD patients develop cognitive impairment and/or dementia over the course of their disease, so that together the LBD represent one of the most important Alzheimer’s Disease Related Dementias (ADRD) affecting the world today.

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