Correlation of behavior changes and BOLD signal in Alzheimer-like rat model.

To explore a potential means for the early diagnosis of Alzheimer disease, we studied the relationship of resting T2* signal and tau hyperphosphorylation/spatial memory deficit. The rat model with tau hyperphosphorylation and spatial memory deficit was established by bilateral hippocampi injection of isoproterenol (IP). Then, the correlative alteration between resting T2* signal and spatial memory retention was assessed with blood oxygenation level dependent (BOLD) functional magnetic resonance imaging (fMRI) study and Morris Water Maze test, and Western blot was employed to confirm tau hyperphosphorylation. The analysis showed following results. (1) Tau phosphorylation at Ser396/Ser404 and Ser199/Ser202 was significantly increased in IP-injected rats as detected by PHF-1 and tau-1, respectively. (2) An AD-like spatial memory retention disturbance was induced at 24 h after isoproterenol injection. (3) A sensitivity threshold of resting T2* signal intensity, which separated the IP-treated rats from vehicle control, was obtained by applying linear regression analysis, and an estimated sensitivity statistical threshold was at 32.62. These results suggest that resting T2* signal may serve as a noninvasive quantitative marker in predicting AD-like spatial memory deficits and tau hyperphosphorylation.