Epidemiological Neuropathology Integrated Studies
Research type
Research Study
Full title
Epidemiological Neuropathology: Integrated Studies of the Cellular and Molecular Pathology of Cognitive Impairment and Frailty in the Ageing Brain in the Cognitive Function and Ageing Study Neuropathology Cohort
IRAS ID
271003
Contact name
Stephen B Wharton
Contact email
Sponsor organisation
University of Sheffield
Clinicaltrials.gov Identifier
Sheffield ref 160283, ARUK-PG2019A-003, Major grant within the protocol
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 Cognitive Function and Ageing Study (CFAS) to investigate the molecular and cellular pathologies of brain ageing, frailty and dementia. Previous CFAS work showed that, whilst 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. Our studies aim to find; 1. Better pathological correlates of dementia by improving measures of known disease-associated pathologies and new markers of pathology, 2. Additional cellular and molecular factors that contribute to cognitive, 3. Cellular mechanisms by which molecular pathologies lead to cell dysfunction and dementia, 4. Compensatory factors that determine how particular pathologies affect cells and thus modulate the effect on cognition, 5. How age-related processes, such as senescence/oxidative stress, contribute to dementia. 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, and methods such as –omics approachs (e.g. proteomics, transcriptomics, epigenomics, metabolomics). Analyses will use statistical approaches and modelling to examine relationships between pathologies and to dementia, and bioinformatics methods to investigate large datasets. Data from all neuropathology studies is archived in the already rich CFAS database, allowing interactions to be studied and adding value by making results available to other investigators. This program of work aims to; 1. Produce better models and explanations for dementia across the ageing spectrum, 2. 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
West Midlands - Edgbaston Research Ethics Committee
REC reference
19/WM/0255
Date of REC Opinion
27 Aug 2019
REC opinion
Favourable Opinion