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PD Heterogeneity

The PD Heterogeneity theme explores the mechanisms behind different manifestations of PD, unpacking variability in disease onset, symptoms, and progression rates. Sub-areas of investigation target the roles of aging, co-pathologies, environmental risk factors, and cellular clearance mechanisms, as well as exploration of factors influencing alpha-synuclein seeding and the neural circuitry behind symptom presentation. By understanding these diverse drivers of disease, this theme aims to propel the field beyond “one-size-fits-all” treatments toward precision medicine tailored to specific patient subtypes.

Our Teams

The focus across these teams will be to explore the mechanisms behind different manifestations of Parkinson’s disease with the goal of moving toward precision medicine tailored to specific patient subtypes.

Aging

Aging

Explore aging-related changes to the immune system and genes, and their role in vulnerability to Parkinson’s disease.

Alpha-synuclein Seeding

Alpha-synuclein Seeding

Characterize the seeding agent driving the alpha-synuclein seeding amplification assay (SAA) — a transformative diagnostic for Parkinson’s disease. By doing so, researchers aim to decode specific disease subtypes and illuminate the systemic biological mechanisms of the disease as it manifests throughout the body.

Circuit Biology

Circuit Biology

Reveal how brain circuits disrupted by pathological alpha-synuclein contribute to symptoms such as sleep disorders and cognitive dysfunction.

Clearance

Clearance

Study the brain’s clearance mechanisms to define how these mechanisms’ breakdown contributes to Parkinson’s and uncover new therapeutics.

Co-pathology

Co-pathology

Understand co-pathologies by investigating how multiple protein abnormalities commonly associated with neurodegenerative diseases such as Alzheimer’s and ALS, including tau, amyloid-beta, and TDP-43, interact with Parkinson’s pathology to drive disease in individual patients.

Environment

Environment

Map environmental risk by studying how exposure to pesticides and air pollution interact with genetics to cause and accelerate Parkinson’s disease, using tools like AI-driven molecular fingerprinting.