In addition, Upstream effect analysis predicted APP (p = 1.46E-08), MAPT (Tau, p = 2.02E-06), PSEN1 (Presenilin-1, p = 2.45E-06) and MKNK1 (MAPK Interacting Serine/Threonine Kinase 1, p = 3.37E-06) as an upstream regulator of the 23 proteins, suggesting the AD/CTE-related pathology for the enhanced levels of these molecules in CTE brain EVs. This evidence concerns the gene PSEN1 and Alzheimer disease.