Accelerated long-term forgetting is a BACE1 inhibitor-reversible incipient cognitive phenotype in Alzheimer's disease model mice.

ABSTRACT:

Aim

After the continued failure of β-secretase (BACE1) inhibitor clinical trials in prodromal as well as mild-to-moderate Alzheimer's disease (AD), they are shifting to further earlier or asymptomatic stages. The aim of this study is to explore a cognitive paradigm that allows us to more sensitively detect beneficial effects of BACE1 inhibitors in presymptomatic AD.

Methods

GRL-8234 (33.4 mg/kg, ip), a small-molecule BACE1 inhibitor, was administered once daily for 28 days to the 5XAFD transgenic mouse model of AD. The contextual fear conditioning was used to evaluate the effects of GRL-8234 on memory deficits in 5XFAD mice at different ages.

Results

Chronic administration of GRL-8234 to 5XFAD mice rescued their contextual memory deficits, when tested 1 day after trai

SUBMITTER: Ohno M 

PROVIDER: S-EPMC8340838 | biostudies-literature | 2021 Jun

REPOSITORIES: biostudies-literature