Loss of Cav-1 in T2DM coincides with alterations in the amyloidogenic pathway and eNOS metabolism. Protein lysate from human brain hippocampal tissue of T2DM and normal aging was analyzed by Western blot. Levels of Cav-1 (A,B) are significantly decreased in the T2DM samples. Levels of BACE-1 (A,C) and FL-APP (A,D) show a trending increase in the T2DM samples, albeit not statistically significant. Levels of Aβ (A,E) are significantly increased in the T2DM cases, and are nondetectable (N.D.) in the normal aging condition. Analysis of downstream signaling of Cav-1 shows a significant decrease in eNOS (F,G), whereas no significant changes in levels of p-Akt, t-Akt, or their ratios were found (F,H,I). N = 3. *p < 0.05 (unpaired t test). **p < 0.01 (unpaired t test).