Figure 1.

Changes in DAGL and monoacylglycerol lipase protein expression in human hippocampus coincide with Alzheimer’s progression. (A) Representative images of molecular targets resolved by western blotting. Data (in kiloDaltons) indicate the calculated molecular weights of the molecules of interest. Solid and open arrowheads identify monoacylglycerol lipase’s 33 kDa and 30 kDa isoforms, respectively. Calculated molecular weights corresponded with those measured in particular experiments in all cases. We did not observe modifications to the molecular weights of any of the targets analysed (otherwise represented as vertical size shifts) when comparing data from control, and cohorts with moderate or severe Alzheimer’s disease [Braak stage III/IV (B2–4) and Braak stage VI (B6), respectively]. Normalized expression (average of controls = 1.0) of CB₁ cannabinoid receptors (CB₁R) (B), DAGLα (C; ⁺P < 0.1), DAGLβ (C₁), ABHD6 (E), 30 kDa (F) and 33 kDa (F₁) isoforms of monoacylglycerol lipase. Individual data points and their colour coding correspond to post-mortem cases listed in Supplementary Table 1. β-actin was used as loading control to normalize our data (Supplementary Fig. 1B and B₁). Horizontal lines represent the mean value of particular patient cohorts. (D) DAGLα and DAGLβ levels correlated positively in controls (not marked), lost correlation in Braak stage III/IV, while exhibited a strong negative expressional relationship in Braak stage VI (red dashed line). (G) Monoacylglycerol lipase isoform expression positively correlates during Alzheimer’s progression. *P < 0.05 (Student’s t-test). 2-AG = 2-arachidonoyl glycerol.