Salk Institute Researchers Create Microprotein Atlas Linking Brain Immune Cell Dysfunction to Alzheimer’s Disease
Researchers at the Salk Institute have developed the first microprotein atlas of the human frontal cortex, both with and without Alzheimer’s disease. This atlas, detailed in a study published in Nature Aging, integrates transcriptomics, mass spectrometry, and deep-learning-predicted spectra from postmortem brain samples to identify microproteins—small proteins typically 150 amino acids or fewer—that have been previously overlooked. The study identified 1,067 uncharacterized microproteins, some of which were expressed differently in Alzheimer’s disease samples, often showing higher overall microprotein expression. Specifically, the researchers focused on microglia, brain immune cells, and found a microprotein at the MKKS locus that was downregulated in Alzheimer’s disease. Knocking out the gene for this microprotein in microglia impaired mitochondrial respiration, suggesting its role in microglial bioenergetics and a potential link between microproteins and immune cell dysfunction in Alzheimer’s.
