featured in recent ARDD2023 video, this goes down with aging (Npc1 in yeast)
https://www.nature.com/articles/s41586-023-06802-1
Given the significant associations between the CognitionBrain age model and several brain aging metrics, we sought to uncover new insights into brain aging mechanisms by examining the proteins that make up the model. A total of 47 of the 49 model proteins were detectable in human brain single-cell RNA sequencing (scRNA-seq) data and most could be mapped to neurons and glia with high specificity (Fig. 3f). Proteins with the largest positive weights in the model (Fig. 3c) included the synaptic proteins complexin 1 (CPLX1), complexin 2 (CPLX2) and neurexin 3 (NRXN3)—which all have genetic links to cognition and AD31,32,33—and stathmin 2 (STMN2) and olfactomedin 1 (OLFM1)—which are involved in neurite outgrowth and axon growth cone collapse34,35. Proteins with large negative weights in the model such as Aldolase Fructose-Bisphosphate C (ALDOC), neuronal pentraxin receptor (NPTXR), carnosine dipeptidase 1 (CNDP1) and Lanc Like Glutathione S-Transferase 1 (LANCL1). ALDOC, NPTXR and CNDP1 are expressed in astrocytes, neurons and oligodendrocytes, respectively (Fig. 3f) and have been proposed as CSF biomarkers for AD36,37. LANCL1, which is primarily expressed in oligodendrocytes (Fig. 3f), has been shown to be crucial for neuronal health in mouse models38. The model also implicated alterations in the glycosylated extracellular matrix through the proteins tenascin R (TNR), neurocan (NCAN) and heparan sulfate-glucosamine 3-sulfotransferase 4 (HS3ST4), underlining the role of the extracellular matrix in brain aging.
