About the Project
VIDA (Vascular and Immune contributors to DementiA) is a multi-institutional partnership between Alzheimer’s Society and four world-leading research sites: the University of Manchester, University of Edinburgh, Imperial, and City St George’s University of London. With projects focusing on the importance of vascular and immune mechanisms in dementia, VIDA PhD students will become the next generation of much-needed dementia researchers, contributing to breakthroughs in dementia diagnosis and treatment.
PhD studentships
VIDA students will embark upon a 4-year fully-funded PhD project at one of the four institutions above, with access to the state-of-the-art research facilities and interdisciplinary training available at all sites. Students at each site will come together as a cohort at several points during the programme, including annual conferences and residential workshop retreats which will link in with other Alzheimer’s Society Doctoral Training Centres across the UK. Students will also participate in engagement schemes with the Alzheimer’s Society and beyond, sharing the impact of their research in the community. The programme also benefits from built in opportunities for placements with leading industrial partners, and bespoke training plans including schemes to develop teaching, mentoring, and grant writing skills.
Project Background
Neurovascular dysfunction is increasingly recognised as a key contributor to Alzheimer’s Disease (AD)1, yet the sequence of vascular events and underlying molecular mechanisms remain unclear. Core abnormalities, such as cerebral hypoperfusion2, blood-brain barrier (BBB) disruption, and impaired cerebrovascular reactivity3, exacerbate amyloid- and tau-associated neurotoxicity. Pericytes, contractile mural cells that support BBB integrity and neurovascular coupling, are particularly vulnerable to amyloid-beta (Aβ) toxicity. Soluble Aβ oligomers induce pericyte contraction and death, leading to BBB leakage and vascular dysfunction4. Plasma and microvascular proteomic studies have identified early endothelial and pericyte stress signatures, including inflammation and oxidative stress, offering mechanistic insight into vascular failure in AD5.
We hypothesise that combining in vivo imaging of pericyte dynamics with plasma and microvascular proteomic profiling in a mouse model of amyloidosis will reveal the chronology and interplay of vascular dysfunction triggered by Aβ toxicity.
The project has two objectives:
(1) to functionally and mechanistically characterise microvascular impairment using two-photon and laser-speckle imaging complemented by ex vivo confocal and light-sheet microscopy; and
(2) to develop MRI-based biomarkers of amyloid-driven vascular dysfunction. Longitudinal MRI will quantify cerebrovascular reactivity, perfusion, and BBB permeability, and these imaging readouts will be correlated with vascular and plasma proteomic molecular signatures to identify robust functional biomarkers.
By establishing the temporal sequence of pericyte degeneration, BBB breakdown, and perfusion deficits over timescales of days to weeks (up to approximately 8 weeks) and linking these to molecular changes, this multidisciplinary project will elucidate the mechanistic drivers of neurovascular dysfunction in AD. The results will provide clinically relevant imaging and molecular biomarkers for early-stage detection and guide translational strategies for diagnosis and therapeutic intervention.
Key details
- Location UK DRI at Edinburgh
- Salary: The studentship is funded through the Alzheimer’s Research UK (ARUK) for 4 years and will cover UK university tuition fees (home fees only). The studentship will also pay an annual stipend based on the standard ARUK set stipend rate.