Investigating notch signalling in patient-derived models of familial Alzheimer's Disease. (360G-Wellcome-211735_Z_18_Z)

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Alzheimer's Disease (AD) is characterised pathologically by extracellular plaques composed of Abeta peptides, which are generated by the successive proteolytic processing of the amyloid precursor protein (APP) by multiple enzymes including the gamma-secretase complex. Human genetics supports a causative role for Abeta in AD: mutations and gene duplications in APP cause familial AD. Further, mutations in PSEN, which forms part of the gamma-secretase complex, are also causative of fAD. However, substantial clinical heterogeneity exists in fAD patients with PSEN1 mutations, the molecular basis of which is not well understood. Our hypothesis is that differential processing of non-APP substrates of gamma secretase may contribute to neurodegeneration in fAD. The aim of this project is to investigate the processing of non-APP substrates of gamma-secretase in fAD, using induced pluripotent stem cell-derived neurons from 7 fAD patients with mutations in APP and PSEN1 and age/sex matched controls. Specifically, we will use western blot to analyse the notch pathway in fAD and control lines and understand if this pathway is dysregulated in AD. This project will allow us to determine if the processing of non-APP substrates of gamma secretase is altered in fAD patient cell models, forming the basis for further mechanistic studies.

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Grant Details

Amount Awarded 0
Applicant Surname Mighell
Approval Committee Internal Decision Panel
Award Date 2018-05-31T00:00:00+00:00
Financial Year 2017/18
Grant Programme: Title Vacation Scholarships
Internal ID 211735/Z/18/Z
Lead Applicant Miss Rebecca Mighell
Partnership Value 0
Planned Dates: End Date 2018-09-29T00:00:00+00:00
Planned Dates: Start Date 2018-07-30T00:00:00+00:00
Recipient Org: Country United Kingdom
Region Greater London