Nature Aging· 2026Q1
A microprotein atlas of the human frontal cortex in Alzheimer’s disease
- 1citations
- Q1SCImago
- 2026year
Short summary
Researchers created a brain microprotein (MP) atlas from over 600 frontal cortex samples, identifying 1,067 MPs not previously cataloged, with spectral evidence. A subset of these MPs are differentially expressed in Alzheimer's disease (AD).
AI-generated from the title and abstract; the full text is not read.
Key points
- Developed a brain microprotein (MP) atlas using transcriptomics, mass spectrometry, and deep learning across >600 frontal cortex samples.
- Identified 1,067 novel MPs with high-confidence spectral support, expanding the annotated brain proteome.
- Found a subset of MPs are differentially expressed in Alzheimer's disease (AD) independently of annotated main ORFs.
- Discovered an MP encoded by MKKS is downregulated in AD and impairs microglial mitochondrial respiration.
AI-generated from the title and abstract; the full text is not read.
Abstract
Understanding the molecular basis of neurodegeneration requires a comprehensive map of the genome's protein-coding output. Although thousands of small open reading frames (ORFs) are translated in the human brain, proteomic evidence for their encoded microproteins (MPs) (≤150 amino acids (aa)) remains limited. Here, we present a brain MP atlas that integrates transcriptomics, mass spectrometry and deep-learning-predicted spectra across more than 600 postmortem frontal cortex samples with and without Alzheimer's disease (AD). We identified 1,067 MPs absent from reviewed UniProtKB entries with high-confidence spectral support. A subset is differentially expressed in AD independently of the annotated main ORF at the same locus. A small ORF expressed by MKKS encodes a 63-amino-acid MP that is the locus's predominant translation product and is downregulated in AD; its loss impairs microglial mitochondrial respiration, implicating it in microglial bioenergetics. This atlas expands the annotated brain proteome and provides a resource for studying MPs in aging and neurodegeneration.
The authors' abstract, as published at the source. Nature Aging, 2026 · DOI ↗
Continue with a free account
Ask the paper: 3 free questions a day about this paper; save it, get its citation, new summaries every day for your field. Takeaways are Premium.
Continue free on the webSign in with Google or Apple; no card needed. You come back to this paper.
On your phone:
Field: Physiology
PhysiologyMedicine