Catalog
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.
A topographical atlas of αSyn dosage and cell-type expression in the mouse brain and periphery
Published: 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. View original preprint.
Persistent hyposmia as surrogate for α-Synuclein-Linked brain pathology
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.
Neuropathological assessment of the olfactory bulb and tract in individuals with COVID-19
Published: 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. View original preprint.
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.
Genetic and pharmacological reduction of CDK14 mitigates α-synuclein pathology in human neurons and in rodent models of Parkinson’s disease
Preprint: Decreasing alpha-synuclein levels is a potential therapeutic approach for synucleinopathies. 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.
3D imaging of neuronal inclusions and protein aggregates in human neurodegeneration by multiscale X-ray phase-contrast tomography
Preprint: This study leverages X-ray phase-contrast tomography for detailed analysis of neurodegenerative diseases focusing on the 3D visualization and quantification of neuropathological features within fixed human postmortem tissue.
Code for analysis of smell test dataset included in: Development of a Simplified Smell Test to Identify Patients with Typical Parkinson’s as Informed by Multiple Cohorts, Machine Learning and External Validation
Code used for the analysis of smell test performance as reported in “Development of a Simplified Smell Test to Identify Patients with Typical Parkinson’s as Informed by Multiple Cohorts, Machine Learning and External Validation,” Li et al., 2024.
Code for clinical dataset analysis included in: Persistent Hyposmia as Surrogate for α-Synuclein-Linked Brain Pathology
Code used for the analysis of clinical data as reported in the study, “Persistent Hyposmia as Surrogate for α-Synuclein-Linked Brain Pathology” in Mollenhauer, Li et al., MedRxiv 2023.
Development of a simplified smell test to identify patients with typical Parkinson’s as informed by multiple cohorts, machine learning and external validation
Reduced olfaction is a common feature of typical Parkinson’s disease (PD) and dementia with Lewy bodies (DLB). The authors created a simplified smell test based on seven specific odorants that can distinguish PD/DLB patients from healthy controls.
Microscopy dataset for: Comparative Analysis of AAV Serotypes for Transduction of Olfactory Sensory Neurons
Imaging dataset for the manuscript, “Comparative Analysis of AAV Serotypes for Transduction of Olfactory Sensory Neurons” by Belfort, Jia et al., 2024.
Comparative analysis of AAV serotypes for transduction of olfactory sensory neurons
This study compared the efficacy and selectivity of 11 different AAV serotypes for the efficient and selective transduction of murine olfactory sensory neurons in vivo. The findings inform research approaches and gene therapy-based initiatives.
Single nucleus transcriptomic dataset of AAV-infected mouse OE
Single nucleus sequencing dataset from mouse murine olfactory epithelium exposed to 4 AAV serotypes via nasal lavage. The goal was to identify the best candidate for transduction of olfactory sensory neurons. Code is included with the dataset.
Computational analysis for “Comparative Analysis of AAV Serotypes for the Transduction of Olfactory Sensory Neurons” by Belfort and Jia et al. 2024
Code for snRNAseq dataset analysis of AAV-infected mouse olfactory epithelium. This code accompanies the manuscript: Comparative Analysis of AAV Serotypes for the Transduction of Olfactory Sensory Neurons by Belfort, Jia et al. 2024.
