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.
For more information please visit our Resources page.
We hypothesize that key factors:
- conformation of aSyn
- interplay with AD pathology
- host features
- locus of early pathology
Determine whether a given LBD individual might develop dementia at outset, after a few years, after decades, or not at all.
We test this hypothesis through four Research Projects supported by four Cores.
Latest News
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Our program is funded by the National Institute on Aging. You can read the full article here.
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Clinical Core Leader Dan Weintraub leads a study investigating long-term dementia risk in Parkinson's disease and finds that dementia in PD occurs less frequently, or later in the disease course, than previous studies have indicated.
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Center investigators Alice Chen-Plotkin and George Kannarkat show that alpha-synuclein conformations in plasma may differ between Parkinson's Disease and Dementia with Lewy Bodies. In collaboration with the David Walt lab at Harvard, center investigators develop methods to measure alpha-synuclein in plasma extracellular vesicles.