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FTLD targets brain regions expressing recently evolved genes.

Lorenzo Pasquini1,2, Felipe L Pereira1, Sahba Seddighi3

  • 1Department of Neurology, Memory and Aging Center, University of California, San Francisco, CA, USA.

Medrxiv : the Preprint Server for Health Sciences
|November 14, 2023
PubMed
Summary

Frontotemporal lobar degeneration (FTLD) affects brain regions with recently evolved genes, particularly those with human accelerated regions (HARs). This study links FTLD subtypes to specific gene expression patterns and evolutionary changes in the brain.

Keywords:
Frontotemporal lobar degenerationTDP-43cryptic exongene expressionhuman accelerated regionstau

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Area of Science:

  • Neuroscience
  • Genomics
  • Evolutionary Biology

Background:

  • Frontotemporal lobar degeneration (FTLD) involves protein aggregation (TDP-43 or tau) linked to social-emotional and language deficits.
  • FTLD's impact on specific brain regions suggests a potential link to genes with unique evolutionary histories in humans.

Conclusions:

  • FTLD preferentially affects brain regions specialized through recent human evolution, indicated by HAR gene expression.
  • Findings suggest a transcriptomic basis for selective vulnerability in different FTLD subtypes.
  • The study highlights the interplay between evolutionary genetics, gene regulation (cryptic splicing), and neurodegeneration in FTLD.