CFAS: Epidemiological Neuropathology
Research type
Research Study
Full title
Cognitive Function and Ageing Studies: Diabetes, Defective Nutrient Signalling and Dementia: an Epidemiological Neuropathology approach.
IRAS ID
184134
Contact name
Stephen B Wharton
Contact email
Duration of Study in the UK
5 years, 0 months, 0 days
Research summary
This program of study uses previously archived autopsy brain tissue from the Medical Research Council Cognitive Function and Ageing Study (CFAS) to investigate the molecular and cellular pathologies of brain ageing, frailty and dementia. Previous studies in CFAS have shown that, whilst classically-defined pathologies such as Alzheimer’s, Lewy body and vascular pathology are the most common causes of dementia, how they result in dementia remains unclear. Furthermore, these neuropathologies do not explain all of dementia; some individuals with very little pathology are demented whilst others with significant pathology are not. Our studies aim to find; 1. Better pathological correlates of dementia by investigating new markers of pathology, 2. Additional cellular and molecular factors that contribute to cognitive impairment either independently of or interacting with classical neuropathologies, 3. Cellular mechanisms by which molecular pathologies lead to cell dysfunction and consequently dementia, 4. Compensatory factors that determine how particular pathologies affect cells and thus modulate the effect on cognition. To do this, we will investigate cellular pathologies of neurons, glia, vascular cells and brain inflammatory response in grey and white matter areas using histological and molecular techniques, including methods such as proteomics and gene expression array methods that allow unbiased investigation of cellular changes and, using bioinformatics methods, relationships between cell types. Data from all studies is archived in the already rich CFAS database, allowing interactions to be studied and adding value by making results available to other investigators. The aims of our work are to; 1. Produce better models and explanations for dementia across the ageing spectrum, 2. This should lead to better data and biomarkers for stratification of dementia (information of value to underpin therapeutic studies in the field). 3. Define new processes and mechanisms of dementia that can lead to new avenues for experimental and therapeutic investigation.
REC name
South West - Frenchay Research Ethics Committee
REC reference
15/SW/0246
Date of REC Opinion
10 Aug 2015
REC opinion
Favourable Opinion