Alzheimer's disease pathology degrades an NMDA receptor-dependent spontaneous activity pattern in cortico-hippocampal circuits - PubMed
6 hours ago
- #Alzheimer's disease
- #NMDAR hypofunction
- #cortico-hippocampal circuits
- Aβ-tau pathology in Alzheimer's disease causes region- and layer-specific impairments in cortico-hippocampal circuits, reducing burst firing in superficial layers and CA1, and mean firing in deep layers and CA1.
- Aβ primes neurons for tau-induced damage; combined Aβ-tau reduces synaptic NMDAR density in both mice and humans, while reducing both restores NMDARs, firing patterns, and improves memory.
- NMDAR antagonism in healthy mice replicates the deficits seen with Aβ-tau pathology, implicating synaptic NMDAR hypofunction as a reversible mechanism linking Aβ-tau synergy to circuit dysfunction in Alzheimer's.