Objective It has been reported that D-galactose （D-gal） can model subacute aging, and aluminum （AI） acts as a neurotoxin, but combined effects of them have not been reported. The present work aimed to reveal the effect of combined administration of D-gal and A1 in mice and compare the effect of D-gal treatment with that of A1 treatment. Meth- ods A1 was intragastricaHy administered and D-gal was subcutaneously injected into Kunming mice for 10 consecutive weeks. Learning and memory, eholinergic systems, as well as protein levels of amyloid β （Aβ） and hyperphosphorylated tau were determined using Morri water maze test, biochemical assays and immunohistochemical staining, respectively. Results The mice with combined treatment had obvious learning and memory deficits, and showed decreases in brain ace- tylcholine （ACh） level and in activities of choline acetyltransferase （CHAT） and acetyleholinesterase （ACHE）. Formation of senile plaque （SP）-like and neurofibrillary tangle （NFT）-like structures was also observed. The behavioral and pathologi- cal changes persisted for at least 6 weeks after withdrawal of D-gal and A1. Conclusion Combined use of D-gal and A1 is an effective way to establish the non-transgenic Alzheimer＇s disease （AD） animal model, and is useful for studies of AD pathogenesis and therapeutic evaluation.
