BACE1 and Alzheimer disease: Chakravarty and Nielsen (1986) also showed that the brains of db/db mice have multiple AD-like properties including impaired cognitive functions, increased phospho-tau and Aβ levels and decreased levels of synaptic proteins, changes that were attenuated by metformin (Li et al., 2012). In contrast to the abovementioned articles, Chen et al. (2009) found that metformin treatment of a transgenic mouse model of AD contributed to the increased expression of BACE1 in an AMPK-dependent manner, which led to an increase in Aβ production.