Objective: To investigate the effects of lithium on cognitive function and metabolism of Amyloid-beta Protein Precursor （APP） and tau phosphorylation in rats chronically exposed to aluminum. Methods: Twenty-four chronically aluminum-exposed rats were randomly divided into 2 groups: a lithium-treatment group and a non-treatment group （n=12 per group）. Lithium chloride was administered to the lithium-treatment group via gastric gavage daily for 6 weeks （200 mg/kg·d LiCl）

while the non-treatment group was administered the same volume of sodium chloride by the same means. An additional control group （n=12） received no intervention. Memory function was evaluated by the Morris water maze test. Aβ was measured by immunohistochemical staining

while total APP

phosphorylated-tau protein

CDK5 and PP2A were determined by Western Blotting. Results: （1） Compared to the non-treatment group

the lithium-treatment group had a significantly shorter mean escape latency and a lower proportion of random navigation pattern in the spatial probe test （P<0.05）. After the platform was taken away

the rats in the lithium-treatment group crossed the platform quadrant significantly more and stayed longer in the platform quadrant than those in the non-treatment group （P<0.05）. （2） The number of Aβ positive neurons in the hippocampus and cortex was significantly less in the lithium-treatment group than in the non-treatment group （P<0.05）

but the content of APP was not different between groups （P=0.730）. （3） Phosphorylation of tau protein decreased significantly in the lithium-treatment group than that in the non-treatment group （P<0.05）. The content of CDK5 in the lithium-treatment group was significantly less than that in the non-treatment group in the cortex and hippocampus

while there was no difference in the content of PP2A between the 2 groups. The expression of CDK5 was significantly correlated with phosphorylated tau （r=0.871

P=0.024） in the lithium-treatment group. Conclusion: Lithium may improve memory function in rats chronically exposed to aluminum by decreasing both the production of Aβ and tau phosphorylation

with the latter results from inhibiting expression of CDK5.