Two new preprints have shed light on the biological aspects of early Alzheimer's disease through proteomic studies. One study, led by Carlos Cruchaga at Washington University in St. Louis and posted on medRxiv on January 13, identified 125 proteins in the CSF that distinguished individuals with inherited familial Alzheimer's disease mutations from those without. Nine of these proteins showed better differentiation between carriers and noncarriers than established CSF Aβ and tau biomarkers. The study focused on participants from the Dominantly Inherited Alzheimer Network cohort who were years or even decades away from displaying symptoms.

Published on January 8 in a bioRxiv preprint, researchers led by Asim Siddiqui at Seer, Inc., in Redwood City, California, and Steven Arnold at Massachusetts General Hospital, Boston, reported on plasma proteins in individuals with sporadic Alzheimer's disease. They found 138 proteins correlated with the disease, including eight associated with cognitive decline, which differed significantly from the proteins identified in the familial Alzheimer's cohort.

The study of the inherited Alzheimer's cohort, which consists of individuals carrying presenilin and APP mutations, revealed 125 proteins showing divergent trajectories in carriers compared to noncarriers. One such protein, SMOC1, was identified as an early potential biomarker, rising 30 years before symptom onset. Machine learning pinpointed nine key proteins, including SMOC1, that accurately identified individuals carrying an Alzheimer's disease mutation. These proteins outperformed traditional biomarkers in distinguishing mutation status, highlighting their potential for early detection.

In contrast, the plasma proteomic analysis of sporadic Alzheimer's disease participants uncovered a different set of proteins, with only one, SMOC1, overlapping with the CSF markers identified in the familial Alzheimer's study. The findings suggest that biomarkers for autosomal dominant Alzheimer's disease may predominantly be found in the CSF, while sporadic cases show more overlap between CSF and blood markers.

The second study, focusing on sporadic Alzheimer's disease, found 100 proteins more abundant and 38 less abundant in individuals with the disease compared to controls. While these plasma proteins did not perform as well as plasma p-tau181 in identifying Alzheimer's patients, some were associated with predicting cognitive decline.

These groundbreaking studies provide valuable insights into early biological changes in Alzheimer's disease and offer hope for the development of novel diagnostic tools for early detection and potential treatment strategies.