A longitudinal analysis of AD patients showed significant differences in the levels of p-Ser312-IRS-1 and p-pan-Tyr-IRS-1 in L1CAM+ EVs as well as the ratio of p-Ser312-IRS-1 to p-pan-tyr-IRS-1 between preclinical and clinical stages up to 10 years before diagnosis, indicating the potential of this blood test to predict the development of AD [92]. Here, L1CAM is linked to Alzheimer disease.