Pathological methamphetamine exposure triggers the accumulation of neuropathic protein amyloid-β by inhibiting UCHL1

•The accumulation of amyloid-β is induced by the exposure of methamphetamine in vivo and in vitro.•Methamphetamine leads to the accumulation of amyloid-β by increasing the stability of BACE1.•The increase of BACE1 induced by methamphetamine is mediated by UCHL1.•Provide new evidence for the connection between methamphetamine abuse and Alzheimer’s disease.