Amyloid induced hyperexcitability in default mode network drives medial temporal hyperactivity and early tau accumulation.
Joseph Giorgio, Jenna N. Adams, A. Maass, William J. Jagust, Michael Breakspear
Neuron December 1, 2023 DOI: 10.1016/j.neuron.2023.11.014 (opens in new tab)
Study at a glance
AI-extracted from the abstract| Characteristics | Observational cohort Peer reviewed |
|---|---|
| Population | Humans with early Alzheimer's disease |
| Topics | Default mode network |
| Key findings | Alzheimer's pathologies flip interactions between the default mode network and the medial temporal lobe from inhibitory to excitatory, with default mode network hyperexcitation predicting tau accumulation in the entorhinal cortex. |
Abstract
In early Alzheimer's disease (AD) β-amyloid (Aβ) deposits throughout association cortex and tau appears in the entorhinal cortex (EC). Why these initially appear in disparate locations is not understood. Using task-based fMRI and multimodal PET imaging, we assess the impact of local AD pathology on network-to-network interactions. We show that AD pathologies flip interactions between the default mode network (DMN) and the medial temporal lobe (MTL) from inhibitory to excitatory. The DMN is hyperexcited with increasing levels of Aβ, which drives hyperexcitability within the MTL and this directed hyperexcitation of the MTL by the DMN predicts the rate of tau accumulation within the EC. Our results support a model whereby Aβ induces disruptions to local excitatory-inhibitory balance in the DMN, driving hyperexcitability in the MTL, leading to tau accumulation. We propose that Aβ-induced disruptions to excitatory-inhibitory balance is a candidate causal route between Aβ and remote EC-tau accumulation.