Hippocampal hyperglutamatergic signaling matters: Early targeting glutamate neurotransmission as a preventive strategy in Alzheimer's disease

This Editorial highlights a remarkable study in the current issue of the Journal of Neurochemistry in which Hascup and coworkers provide novel data showing that riluzole, an anti‐glutamatergic drug, may be a promising early intervention strategy for Alzheimer's disease (AD), aimed at restoring glutamate neurotransmission prior to amyloid beta (Aβ) plaque accumulation and cognitive decline. The mice APP/PS1, a model of AD, initially are cognitively normal but have elevated glutamate release in the hippocampus at 2–4 months of age. They begin showing cognitive decline and Aβ plaque accumulation at approximately 6–8 months of age, and show obvious AD neuropathology and cognitive impairment at 10–12 months. The riluzole treatment over 4 months (at 2–6 months of age) targeting early changes in glutamatergic neurotransmission prevents cognitive decline observed at 12 months of age and restores glutamatergic neurotransmission. This is one of the most convincing preclinical evidence supporting the idea of targeting glutamate neurotransmission in patients at risk for AD and to use riluzole for this purpose. APP/PS1 mice, a model of Alzheimer's disease (AD), have elevated glutamate release in the hippocampus at 2–4 months of age. This Editorial highlights a study by Findley and coworkers published in the current issue of the Journal of Neurochemistry, in which the authors start by showing cognitive decline and Aβ plaque accumulation at 6–8 months, and show evident AD neuropathology and cognitive impairment at 10–12 months. Prodromal riluzole treatment over 4 months restores glutamatergic neurotransmission and prevents cognitive decline observed at 12 months. These findings confirm the validity of targeting glutamate neurotransmission in patients at risk for AD and suggest that riluzole, a clinically used drug, may be used for the implementation of this new strategy. This Editorial highlights the article:https://doi.org/10.1111/jnc.15224