We have described a novel excitotoxic process potentially relevant to AD in which hypofunctional NMDA receptors cease driving GABAergic neurons that cease inhibiting the 2 major excitatory transmitters in the brain (glutamate and acetylcholine), and these disinhibited excitatory transmitters then act in concert to slowly hyperstimulate neurons in corticolimbic brain regions to death. Accepting this hypothesis that features a multisystem network disturbance that can explain how a corticolimbic pattern of neurodegenerative events is triggered in AD does not require abandoning other candidate mechanisms. For example, genetic hypotheses that focus primarily on amyloid processing or deposition are compatible with our hypothesis and would gain in explanatory power if combined with our hypothesis. If our hypothesis is correct, it may provide valuable new therapeutic approaches to AD.
|Number of pages||7|
|Journal||Archives of neurology|
|State||Published - Oct 1997|