ASAP is committed to accelerating the pace of discovery and informing a path to a cure for Parkinson’s disease through collaboration, research-enabling resources, and data sharing. We’ve created this catalog to showcase the research outputs and tools developed by ASAP-funded programs.
Synaptic location is a determinant of the detrimental effects of α-synuclein pathology to glutamatergic transmission in the basolateral amygdala
αSyn expression is restricted in a subset of glutamatergic synapses in BLA and its aggregation decreases cortico-BLA transmission through both gained toxicity and loss of normal function. These results might be relevant to the reduced cortical control of amygdala function that has been associated with psychiatric deficits in PD.
Preprint: Parkinson’s disease (PD) is the second most common neurodegenerative disease worldwide and presents pathologically with Lewy pathology and dopaminergic neuron loss. This atlas provides much-needed insight into the cellular topography of αSyn, and provides a quantitative map to test assumptions about the role of αSyn in network vulnerability in PD and other αSynucleinopathies.
Preprint: The team identified significant age- and posit that simple-to-administer, quantitative smell tests could serve as inexpensive screening tools in future population studies for the identification of α-synuclein-related brain disorders, including Parkinson’s during its premotor phase.
The team concluded from their autopsy series that after a fatal course of COVID-19, microscopic changes, when present, in the rostral, intracranial portion of the olfactory circuitry generally reflected neurodegenerative processes seen elsewhere in the brain. In general, inflammation correlated best with the degree of Alzheimer’s-linked tauopathy and declined with progression of age in COVID19+ patients.
Constitutive nuclear accumulation of endogenous alpha-synuclein in mice causes motor impairment and cortical dysfunction, independent of protein aggregation
Published: Nuclear alpha-synuclein may play a role in the pathogenesis of PD. To study this, the authors engineered SncaNLS mice that exhibit endogenous alpha-synuclein in the nucleus. After behavioral, histological, and biochemical analysis of the mice, the authors found that chronic nuclear alpha-synuclein can create toxic cellular phenotypes, independent of aggregation.
Preprint: Decreasing alpha-synuclein levels is a potential therapeutic approach for synuleinopathies. The authors identified CDK14 regulates alpha-synuclein and show reduction of CDK14 in two different PD mouse models reduces alpha-synuclein and PD-like characteristics. They also demonstrate that inhibiting CDK14 with a drug lowers alpha-synuclein burdens in rodent and human neurons.