Amyloid induced hyperexcitability in default mode network drives medial temporal hyperactivity and early tau accumulation.
Neuron December 1, 2023 Joseph Giorgio, Jenna N. Adams, A. Maass et al.
In early Alzheimer's disease, amyloid-beta deposits appear throughout association cortex while tau appears in the entorhinal cortex, but why these pathologies initially arise in different locations is unclear. Using task-based fMRI and multimodal PET imaging, the authors show that Alzheimer's pathologies flip interactions between the default mode network and the medial temporal lobe from inhibitory to excitatory. The default mode network becomes hyperexcited with increasing amyloid-beta levels, which drives hyperexcitability within the medial temporal lobe, and this directed hyperexcitation predicts the rate of tau accumulation within the entorhinal cortex. The results support a model where amyloid-beta-induced disruptions to local excitatory-inhibitory balance in the default mode network drive medial temporal lobe hyperexcitability, leading to tau accumulation.