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Imaging and activation of glymphatic clearance: a novel strategy for Alzheimer’s Disease (360G-Wellcome-204624_Z_16_Z)

There is a critical need for early and accurate biomarkers of the pre-symptomatic phase of Alzheimer's disease (AD), to maximise the efficacy of emerging therapies. Recent evidence implicates cerebral glymphatic exchange as a key mechanism in early AD pathogenesis [Figure 1] [1-4]. I will develop the first non-invasive method for the quantitative assessment of glymphatic clearance, using MRI. These novel methods will be carefully validated by comparison with the invasive measures [5], that I have previously established, in normal, aged and AQP4 null mice. I will apply these novel techniques longitudinally to mouse models of ageing and AD (amyloid and tau) to investigate impairment of glymphatic clearance relative to more established markers of AD pathogenesis such as structural imaging, perfusion and histological assessment of plaque/tangle burden. As such, these data will be the first to elucidate the chronology of abnormal glymphatic clearance in AD pathogenesis. Finally, I will combine these methods with targeted optogenetics to assess the interaction of vessel tone and vasomotion to rates of glymphatic clearance in order to characterise the underlying mechanisms that drive CSF-ISF exchange.

£780,158

26 Oct 2016

Grant details
Amount Awarded 780158
Applicant Surname Wells
Approval Committee Sir Henry Dale Fellowship Interview Committee
Award Date 2016-10-26T00:00:00+00:00
Financial Year 2016/17
Grant Programme: Title Sir Henry Dale Fellowship
Internal ID 204624/Z/16/Z
Lead Applicant Dr Jack Wells
Planned Dates: End Date 2022-02-28T00:00:00+00:00
Planned Dates: Start Date 2017-03-01T00:00:00+00:00
Recipient Org: Country United Kingdom
Region Greater London
Sponsor(s) Prof Raymond MacAllister
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