Adenosine deficiency facilitates CA1 synaptic hyperexcitability in the presymptomatic phase of a knockin mouse model of Alzheimer disease.

ABSTRACT: The disease's trajectory of Alzheimer disease (AD) is associated with and negatively correlated to hippocampal hyperexcitability. Here, we show that during the asymptomatic stage in a knockin (KI) mouse model of Alzheimer disease (APP^{NL-G-F/NL-G-F}; APPKI), hippocampal hyperactivity occurs at the synaptic compartment, propagates to the soma, and is manifesting at low frequencies of stimulation. We show that this aberrant excitability is associated with a deficient adenosine tone, an inhibitory neuromodulator, driven by reduced levels of CD39/73 enzymes, responsible for the extracellular ATP-to-adenosine conversion. Both pharmacologic (adenosine kinase inhibitor) and non-pharmacologic (ketogenic diet) restorations of the adenosine tone successfully normalize hippocampal neuronal a

SUBMITTER: Bonzanni M 

PROVIDER: S-EPMC11754081 | biostudies-literature | 2025 Jan

REPOSITORIES: biostudies-literature