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Prof Bettina Platt, Dr Gernot Riedel
No more applications being accepted
Funded PhD Project (European/UK Students Only)
About the Project
Supervisors: Prof Bettina Plat, Prof Gernot Riedel, Dr H Seton & Prof Andy Welch
Key neuropathological hallmarks of Alzheimer’s disease (AD) are the accumulation of β-amyloid and hyperphosphorylated tau, which can be mimicked in experimental models. We have recently generated novel transgenic models (PLB lines) based on the over-expression of human mutated amyloid precursor protein (APP), tau and/or presenilin genes (PS1). Phenotypes comprise age-related cognitive impairments and histopathology of intra-neuronal amyloid and hyperphosphorylated tau accumulation in hippocampus and cortex, paralleled by dorsal hypometabolism that can be visualised with metabolic 18FDG/PET imaging, alongside deficits in short-term and long-term synaptic plasticity (see Platt et al, 2011a&b). While the gross phenotype of this model is now established, the present project seeks to develop advanced translational procedures with better anatomical precision. Therefore, combined functional PET and structural MRI imaging studies will be conducted that enable metabolic and anatomical data to be mapped to brain regions involved in (failing) learning and memory, as well as identify correlations with tau and amyloid pathologies. PET and MRI imaging will be followed by post-mortem identification of histological changes. We aim to identify how specific AD-related genes and resulting pathologies contribute to, and correlate with, metabolic and structural deteriorations in murine models of AD, thus determining their contribution to imaging phenotypes.
Aims:
(1) Identify and correlate functional (FDG-PET) and structural (MRI) alterations in PLB models.
(2) Confirm and correlate AD-like histo-pathologies (amyloid- & tau-related, inflammation, atrophy) with imaging phenotypes.
(3) Optimise image analyses and anatomical precision.
(4) Develop a mouse brain atlas for preclinical imaging procedures.
Key neuropathological hallmarks of Alzheimer’s disease (AD) are the accumulation of β-amyloid and hyperphosphorylated tau, which can be mimicked in experimental models. We have recently generated novel transgenic models (PLB lines) based on the over-expression of human mutated amyloid precursor protein (APP), tau and/or presenilin genes (PS1). Phenotypes comprise age-related cognitive impairments and histopathology of intra-neuronal amyloid and hyperphosphorylated tau accumulation in hippocampus and cortex, paralleled by dorsal hypometabolism that can be visualised with metabolic 18FDG/PET imaging, alongside deficits in short-term and long-term synaptic plasticity (see Platt et al, 2011a&b). While the gross phenotype of this model is now established, the present project seeks to develop advanced translational procedures with better anatomical precision. Therefore, combined functional PET and structural MRI imaging studies will be conducted that enable metabolic and anatomical data to be mapped to brain regions involved in (failing) learning and memory, as well as identify correlations with tau and amyloid pathologies. PET and MRI imaging will be followed by post-mortem identification of histological changes. We aim to identify how specific AD-related genes and resulting pathologies contribute to, and correlate with, metabolic and structural deteriorations in murine models of AD, thus determining their contribution to imaging phenotypes.
Aims:
(1) Identify and correlate functional (FDG-PET) and structural (MRI) alterations in PLB models.
(2) Confirm and correlate AD-like histo-pathologies (amyloid- & tau-related, inflammation, atrophy) with imaging phenotypes.
(3) Optimise image analyses and anatomical precision.
(4) Develop a mouse brain atlas for preclinical imaging procedures.
Funding Notes
Funding
Full funding is available to UK/EU candidates only.
Eligibility
Candidates should have (or expect to achieve) a First Class or 2.1 Honours degree (or equivalent) in a relevant discipline.
Full funding is available to UK/EU candidates only.
Eligibility
Candidates should have (or expect to achieve) a First Class or 2.1 Honours degree (or equivalent) in a relevant discipline.
References
Platt B, Drever B, Koss D, Stoppelkamp S, Jyoti A, Plano A, Utan A, Merrick G, Ryan D, Melis V, Wan H, Mingarelli M, Porcu E, Scrocchi L, Welch A, Riedel G. Abnormal Cognition, Sleep, EEG and Brain Metabolism in a Novel Knock-In Alzheimer Mouse, PLB1. PLoS One. 2011;6(11):e27068. Epub 2011 Nov 11.
Platt B, Welch A and Riedel G.. 18FDG-PET imaging, EEG and sleep phenotypes as translational biomarkers for research in Alzheimer's disease. Biochem Soc Trans (2011), 39:874-880.
Mingarelli, M., Welch, A., Arthur, M., Wan, H., Riedel, G. and Platt, B., 2009. The first 3rd generation Alzheimer mouse, PLB1: A FDG-PET study. Alzheimer & Dementia, 5(4), P7 & P436.
Platt B, Welch A and Riedel G.. 18FDG-PET imaging, EEG and sleep phenotypes as translational biomarkers for research in Alzheimer's disease. Biochem Soc Trans (2011), 39:874-880.
Mingarelli, M., Welch, A., Arthur, M., Wan, H., Riedel, G. and Platt, B., 2009. The first 3rd generation Alzheimer mouse, PLB1: A FDG-PET study. Alzheimer & Dementia, 5(4), P7 & P436.
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