Active Brain & Nervous System Psychology & Behaviour

Exploring the pathways through which amyloid/tau co-pathology impacts dementia in Parkinson's Disease

Funder Wellcome Charity-funded
Recipient organisation University College London
Funding Not disclosed
Period Oct 2025 — Sept 2028

In plain English

AI plain-English summary

Half of all Parkinson’s patients develop dementia within a decade of diagnosis, and this project will track the brain changes that drive that decline. The problem is that doctors cannot predict which Parkinson’s patients will lose their memory and thinking skills, or why. The usual suspect in Parkinson’s is a protein called α-synuclein, but many patients also accumulate sticky clumps of amyloid and tangled tau—the same proteins linked to Alzheimer’s. This project asks whether those co-occurring pathologies, not α-synuclein alone, are what tip the brain into dementia. The researcher will combine three approaches. First, she will mine a large dataset of brain scans, spinal fluid, genetics, and cognitive tests from patients at different disease stages, looking for links between amyloid, tau, and disrupted brain wiring. Second, she will use mice with single and combined pathologies, recording brain activity with ultrasound and neural probes to see how each protein affects memory circuits. Third, she will grow human brain organoids to study how Parkinson’s pathology disrupts the cholinergic network—a system critical for memory. This is fundamental science. If it succeeds, it will clarify which protein combinations drive dementia in Parkinson’s, potentially guiding future trials that target the right pathology in the right patient.

View original technical description
Approximately 50% of Parkinson’s patients go on to develop dementia within 10 years from their Parkinson’s diagnosis. The factors which predict cognitive progression for Parkinson’s patients are currently poorly understood. In this project, I will apply a multimodal approach to study the mechanisms contributing to cognitive decline in Parkinson’s. The first part of the project will use a large dataset of multimodal MRI, amyloid and tau PET, genetic, lumbar puncture, cognitive and lifestyle data from patients at different stages of disease progression. I will use these data to explore the link between the risk of dementia, tau deposition and aberrant structural connectivity and how this is impacted by interaction with increased amyloidosis and presence of α-synuclein. In the second part of the project I will employ mouse models, using wild type mice as well as mice with Aβ, tau and combined pathology, using functional ultrasound along with electrophysiology recordings from neural probes to explore the mechanisms through which these pathologies affect cognitive performance. Finally, I will use an organoid-based in-vitro model to study cholinergic network function in neuronal circuits associated with memory, employing this model to explore how network function is affected by Parkinson’s pathology including α-synuclein, Aβ and tau.

View the original record at the funder ↗

Researchers

Steven Allsopp (EPMC Awardee)

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Original classification

PhD Studentship (Basic)

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