APOE4 brains for aggregate analysis
Research type
Research Study
Full title
Single-Molecule Characterization of α-synuclein, β-amyloid and Tau Aggregates in Alzheimer's disease APOE4 brains
IRAS ID
363334
Contact name
David Klenerman
Contact email
Sponsor organisation
University of Cambridge
Duration of Study in the UK
2 years, 11 months, 30 days
Research summary
95% of AD cases are defined as sporadic, not accounted by causative genes (Alzheimer’s Association), but risk genes have been identified that increase propensity to develop sporadic AD. The apolipoprotein E4 (ApoE4) variant is the single greatest genetic risk factor for sporadic AD . ApoE is encoded by the APOE gene, located on chromosome 19. It exists in three major isoforms—ApoE2, ApoE3, and ApoE4—arising from single nucleotide polymorphisms (SNPs) within three different alleles . Among these isoforms, ApoE4 is strongly associated with increased risk (up to 15-fold increase of AD than ApoE3 homozygotes) for both EOAD and LOAD. ApoE3 is the most common isoform in the general population, whereas ApoE2 appears to exert a protective effect against AD .The relationship between APOE and disease pathology is still poorly understood. In neuropathology, aggregated beta-amyloid and hyperphosphorylated tau are the two main hallmarks of AD alongside neuroinflammation. Characterising the influence of APOE genotype on protein aggregation and inflammation could be central to the development of new diagnostic, monitoring or therapeutic tools for AD. By measuring protein aggregate composition, size, shape and quantity (tau and beta-amyloid) we are beginning to better understand which aggregates are formed at different stages of disease, in which brain regions, and by which mechanisms they are biologically damaging.
Here, we aim to report the effect of APOE genotype upon protein aggregate characteristics in AD progression, and thus hope to uncover new mechanisms underlying APOE’s link to AD risk, in particular the molecular mechanisms by which ApoE4 increases the risk of developing Alzheimer’s disease.
REC name
Wales REC 5
REC reference
25/WA/0304
Date of REC Opinion
2 Oct 2025
REC opinion
Favourable Opinion