Better Brain Fitness (a Brainjo Production) An Existential Crisis for Alzheimer's Research?
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Feb 28, 2026 A recent PLOS One study comparing living and postmortem brain tissue sparks debate about large molecular differences. Discussion covers RNA splicing and protein expression contrasts found in samples from DBS surgeries. They debate whether postmortem signals reflect dying processes and how that might skew Alzheimer’s research. Ideas for replication, paired sampling, and animal studies are proposed.
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Postmortem Brains Differ Radically From Living Tissue
- Postmortem brain tissue shows massive molecular differences from living brain tissue across RNA splicing and protein expression.
- The PLOS One study found ~74% of primary transcripts, ~70% of mature transcripts, and 61% of proteins differed between living DBS samples (n=275) and matched postmortem samples.
Death Creates A Misleading Molecular Story
- Death appears to reorganize the molecular landscape so postmortem signatures may reflect dying rather than disease mechanisms.
- Josh Turknett used a flood-and-crime-scene analogy: postmortem changes can create a coherent but misleading story about what actually happened.
Alzheimer's Models May Be Built On Red Herrings
- If postmortem signals reflect dying, decades of Alzheimer's models based on dead tissue may point researchers toward red herrings.
- Josh Turknett argued this could be a key reason pharmaceutical approaches for Alzheimer's have repeatedly failed.