Target Identification for Brain Resilience
Research type
Research Study
Full title
Target identification for brain resilience
IRAS ID
365798
Contact name
Ravi Solanki
Contact email
Sponsor organisation
Prima Mente
Duration of Study in the UK
5 years, 0 months, 1 days
Research summary
Alzheimer’s disease is characterised by progressive cognitive decline, yet a subset of individuals exhibits resilience, maintaining cognition despite significant neuropathology. While genetic and transcriptomic studies have provided insights into AD mechanisms, the proteome, the functional mediator of cellular processes, remains under-explored, particularly in resilient brains. Proteomic profiling across multiple brain regions can reveal molecular networks that support neuronal survival and synaptic integrity.
This project aims to identify protein-level signatures and pathways underlying neuronal resilience by analysing post-mortem brain tissue from 90 donors: 30 healthy controls, 30 resilient individuals, and 30 AD patients. Four regions will be studied per donor: entorhinal cortex, hippocampus, dorsolateral prefrontal cortex and occipital cortex. These regions are selected due to their critical roles in memory formation, executive function, and their differential vulnerability in AD.
Quantitative proteomics will be performed using Tandem Mass Tag (TMT) labeling with high-resolution, data-dependent acquisition (DDA) mass spectrometry for multiplexed protein quantification, complemented by data-independent acquisition (DIA) MS to increase proteome coverage and reproducibility. Both bulk and single-cell proteomics approaches will be applied to capture population-level and cell-type-specific protein dynamics. Data will be integrated with machine learning models to identify protein modules associated with resilience, predict regulatory targets, and guide downstream perturbation experiments in iPSC-derived neurons.
The requested frozen tissue is essential to preserve protein integrity for high-quality proteomics. The study will advance understanding of protective mechanisms in the human brain, revealing potential therapeutic targets to maintain neuronal function. By uncovering resilience pathways, this research could inform novel strategies to prevent or delay neurodegenerative disease, ultimately improving outcomes for patients and their carers.
REC name
West Midlands - South Birmingham Research Ethics Committee
REC reference
25/WM/0266
Date of REC Opinion
22 Dec 2025
REC opinion
Further Information Favourable Opinion