Journal Article

DZNE-2024-00215

http://join2-wiki.gsi.de/foswiki/pub/Main/Artwork/join2_logo100x88.png Amyloid induced hyperexcitability in default mode network drives medial temporal hyperactivity and early tau accumulation.

Giorgio, J. ; Adams, J. N. ; Maass, A.DZNE* ; Jagust, W. J. ; Breakspear, M.

2024
Elsevier New York, NY

This record in other databases:    

Please use a persistent id in citations: doi:10.1016/j.neuron.2023.11.014

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.

Keyword(s): Humans (MeSH) ; tau Proteins: metabolism (MeSH) ; Default Mode Network (MeSH) ; Alzheimer Disease: pathology (MeSH) ; Amyloid beta-Peptides: metabolism (MeSH) ; Entorhinal Cortex: metabolism (MeSH) ; Magnetic Resonance Imaging (MeSH) ; Positron-Emission Tomography (MeSH) ; Alzheimer’s disease ; Alzheimer’s disease ; Alzheimer’s disease ; amyloid ; fMRI ; functional connectivity ; preclinical Alzheimer’s disease ; tau ; tau Proteins ; Amyloid beta-Peptides ; preclinical Alzheimer’s disease ; preclinical Alzheimer’s disease

---

Contributing Institute(s):

1. Multimodal Neuroimaging (AG Maaß)

Research Program(s):

1. 353 - Clinical and Health Care Research (POF4-353) (POF4-353)

Appears in the scientific report 2024

---

Database coverage:
; ; ; BIOSIS Previews ; Biological Abstracts ; Clarivate Analytics Master Journal List ; Current Contents - Life Sciences ; Ebsco Academic Search ; Essential Science Indicators ; IF >= 15 ; JCR ; Nationallizenz ; SCOPUS ; Science Citation Index Expanded ; Web of Science Core Collection

---