Alzheimer's Disease Associated With Mitochondrial Microprotein Variants

Researchers at the University of Southern California, the Salk Institute for Biological Sciences, and elsewhere outline a role in Alzheimer's disease (AD) risk for a small protein dubbed SHMOOSE, found by using mass spectrometry and other experiments that followed up on an Alzheimer's-associated SNP in mitochondrial DNA. As they report in Molecular Psychiatry, cerebrospinal fluid (CSF) levels of SHMOOSE appear to track with everything from age to tau levels and white matter features in the brain, while alterations affecting the newly described mitochondrial microprotein appear to correspond with a 20 percent to 50 percent increase in AD risk. In a series of follow-up experiments, the authors saw transcriptome shifts in the rat hypothalamus by RNA sequencing after administering the SHMOOSE microprotein to the brain, as well as increase expression of the microprotein in post-mortem brain samples from individuals with AD, among other apparent brain effects. "[W]e showed mitochondrial DNA variants can associate with several related neurobiological phenotypes," they report, adding that "correlation among CSF levels of SHMOOSE, CSF AD-related biomarkers (e.g., tau), and brain white matter suggests SHMOOSE has potential as a biomarker."