Preprint reports mRNA editing may alter APOE isoform expression in the human brain
A bioRxiv preprint presents evidence that some individuals express brain APOE transcripts that differ from their genomically encoded allele, raising questions about how APOE risk variants are expressed.
A preprint posted to bioRxiv reports that the risk status assigned to individuals by their genomic APOE allele may not fully capture the APOE protein isoforms present in the brain. The authors show that a subset of individuals express APOE transcripts carrying C-to-T variants at one or both of the two sites that distinguish the three major APOE alleles (ε2, ε3, and ε4) — and that in some cases these transcript-level variants differ from what is encoded in the individual's genomic DNA.
The authors propose that mRNA editing — post-transcriptional modification of RNA bases — could be responsible, a mechanism that has previously been documented at other loci in the human brain. If confirmed, this would mean that some individuals classified as APOE ε3/ε3 by genomic sequencing could be producing a proportion of APOE ε4-like or APOE ε2-like protein in neural tissue, and vice versa.
APOE ε4 is the most strongly established common genetic risk factor for late-onset Alzheimer's disease. The question of whether mRNA editing modulates effective APOE isoform status in the brain has significant implications for research into disease mechanisms and for interpretation of APOE genotyping results in research contexts.
This is a preprint and has not been peer-reviewed. Findings should be regarded as preliminary pending independent replication and formal review. The work intersects with a separate cluster in this batch (item [33], PLOS Genetics) examining APOE isoform biology across environmental contexts; the two items are kept separate as they address distinct questions.
Plain-language version
For patients, families, and general readers. Educational only — not medical advice.
The APOE gene comes in several versions, or alleles, that affect a person's risk of developing Alzheimer's disease. It has long been assumed that the version of APOE a person has in their DNA is the version their body uses. A new scientific report — not yet checked by independent experts — suggests this may not always be the case. The researchers found that some people's brain cells appear to produce a slightly different form of the APOE protein than their DNA would predict, possibly because of a process called RNA editing, which can alter the molecular messages cells use to make proteins. If this finding holds up after further checking, it could change how researchers think about APOE and Alzheimer's risk. This work is at an early stage and has not yet been peer-reviewed. It does not change current guidance about genetic testing or Alzheimer's prevention. This is an educational summary, not medical advice. If anything here raises questions for you, please speak with your GP or a clinical professional.
Sources
Read the original reporting — these are the public sources this summary draws from.
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Primary sourcePreprint bioRxiv (Cold Spring Harbor Laboratory) · 2026-09-09mRNA editing of the Alzheimer's risk gene APOE