Hippocampal hyperactivity in a rat model of Alzheimer’s disease DOI Creative Commons

Liudmila Sosulina,

Manuel Mittag,

Hans‐Rüdiger Geis

et al.

Journal of Neurochemistry, Journal Year: 2021, Volume and Issue: 157(6), P. 2128 - 2144

Published: Feb. 14, 2021

Neuronal network dysfunction is a hallmark of Alzheimer's disease (AD). However, the underlying pathomechanisms remain unknown. We analyzed hippocampal micronetwork in transgenic McGill-R-Thy1-APP rats (APPtg) at beginning extracellular amyloid beta (Aβ) deposition. established two-photon Ca2+ -imaging vivo hippocampus and found hyperactivity CA1 neurons. Patch-clamp recordings brain slices vitro revealed increased neuronal input resistance prolonged action potential width pyramidal did neither observe changes synaptic inhibition, nor excitation. Our data support view that intrinsic excitability neurons may precede inhibitory an early stage Aβ-deposition progression.

Language: Английский

Neuronal excitation/inhibition imbalance: core element of a translational perspective on Alzheimer pathophysiology DOI Creative Commons
Fernando Maestú, Willem de Haan, Marc Aurel Busche

et al.

Ageing Research Reviews, Journal Year: 2021, Volume and Issue: 69, P. 101372 - 101372

Published: May 21, 2021

Our incomplete understanding of the link between Alzheimer's Disease pathology and symptomatology is a crucial obstacle for therapeutic success. Recently, translational studies have begun to connect dots protein alterations deposition, brain network dysfunction cognitive deficits. Disturbance neuronal activity, in particular an imbalance underlying excitation/inhibition (E/I), appears early AD, can be regarded as forming central structural dysfunction. While there are emerging (non-)pharmacological options influence this imbalance, complexity human dynamics has hindered identification optimal approach. We suggest that focusing on integration neurophysiological aspects AD at micro-, meso- macroscale, with support computational modeling, unite fundamental clinical knowledge, provide general framework, rational targets.

Language: Английский

Citations

147
Targeting neuroinflammation in Alzheimer’s disease: from mechanisms to clinical applications DOI Creative Commons

Yu Liu,

Zizhen Si,

Chen-Jun Zou

et al.

Neural Regeneration Research, Journal Year: 2022, Volume and Issue: 18(4), P. 708 - 708

Published: Sept. 21, 2022

Alzheimer's disease is characterized by sustained neuroinflammation leading to memory loss and cognitive decline. The past decade has witnessed tremendous efforts in research; however, no effective treatment available prevent progression. An increasing body of evidence suggests that plays an important role pathogenesis, alongside the classical pathological hallmarks such as misfolded aggregated proteins (e.g., amyloid-beta tau). Firstly, this review summarized clinical characteristics disease. Secondly, we outlined key aspects glial cell-associated inflammation pathogenesis provided latest on roles microglia astrocytes pathology. Then, revealed double-edged nature inflammatory cytokines inflammasomes In addition, potential therapeutic innate immunity for were also discussed through these mechanisms. final section, remaining problems according current research status discussed.

Language: Английский

Citations

111
Altered excitatory and inhibitory neuronal subpopulation parameters are distinctly associated with tau and amyloid in Alzheimer’s disease DOI Creative Commons
Kamalini G. Ranasinghe, Parul Verma, Chang Cai

et al.

eLife, Journal Year: 2022, Volume and Issue: 11

Published: May 26, 2022

Neuronal- and circuit-level abnormalities of excitation inhibition are shown to be associated with tau amyloid-beta (Aβ) in preclinical models Alzheimer's disease (AD). These relationships remain poorly understood patients AD.Using empirical spectra from magnetoencephalography computational modeling (neural mass model), we examined excitatory inhibitory parameters neuronal subpopulations investigated their specific associations regional Aβ, measured by positron emission tomography, AD.Patients AD showed abnormal time-constants neural gains compared age-matched controls. Increased distinctly correlated higher depositions while increased Aβ depositions.Our results provide critical insights about potential mechanistic links between oscillations cellular correlates impaired synaptic functions AD.This study was supported the National Institutes Health grants: K08AG058749 (KGR), F32AG050434-01A1 K23 AG038357 (KAV), P50 AG023501, P01 AG19724 (BLM), P50-AG023501 (BLM GDR), R01 AG045611 (GDR); AG034570, AG062542 (WJ); NS100440 (SSN), DC176960 DC017091 AG062196 (SSN); a grant John Douglas French Foundation (KAV); grants Larry L. Hillblom Foundation: 2015-A-034-FEL 2019-A-013-SUP (KGR); Association: AARG-21-849773 PCTRB-13-288476 made possible Part CloudTM (ETAC-09-133596); Tau Consortium (GDR WJJ), gift S. D. Bechtel Jr. Foundation.

Language: Английский

Citations

84
Connectome-based modelling of neurodegenerative diseases: towards precision medicine and mechanistic insight DOI
Jacob W. Vogel, Nick Corriveau‐Lecavalier, Nicolai Franzmeier

et al.

Nature reviews. Neuroscience, Journal Year: 2023, Volume and Issue: 24(10), P. 620 - 639

Published: Aug. 24, 2023

Language: Английский

Citations

77
Alzheimer’s disease as a synaptopathy: Evidence for dysfunction of synapses during disease progression DOI Creative Commons
S. Meftah, Jian Gan

Frontiers in Synaptic Neuroscience, Journal Year: 2023, Volume and Issue: 15

Published: March 9, 2023

The synapse has consistently been considered a vulnerable and critical target within Alzheimer’s disease, loss is, to date, one of the main biological correlates cognitive decline disease. This occurs prior neuronal with ample evidence that synaptic dysfunction precedes this, in support idea failure is crucial stage disease pathogenesis. two pathological hallmarks abnormal aggregates amyloid or tau proteins, have had demonstrable effects on physiology animal cellular models There also growing these proteins may synergistic effect neurophysiological dysfunction. Here, we review some findings alterations what know from models. First, briefly summarize human suggest synapses are altered, including how this relates network activity. Subsequently, considered, highlighting mouse pathology role play dysfunction, either isolation examining pathologies interact specifically focuses function observed models, typically measured using electrophysiology calcium imaging. Following loss, it would be impossible imagine not alter oscillatory activity brain. Therefore, discusses underpin aberrant patterns seen patients. Finally, an overview key directions considerations field covered. includes current therapeutics targeted at but methods modulate rescue patterns. Other important future avenues note include non-neuronal cell types such as astrocytes microglia, mechanisms independent will certainly continue for foreseeable future.

Language: Английский

Citations

73
Moving beyond amyloid and tau to capture the biological heterogeneity of Alzheimer’s disease DOI Creative Commons
Tracy L. Young‐Pearse, Hyo Lee, Yi‐Chen Hsieh

et al.

Trends in Neurosciences, Journal Year: 2023, Volume and Issue: 46(6), P. 426 - 444

Published: April 3, 2023

Language: Английский

Citations

49
Amyloid induced hyperexcitability in default mode network drives medial temporal hyperactivity and early tau accumulation DOI Creative Commons
Joseph Giorgio, Jenna N. Adams, Anne Maaß

et al.

Neuron, Journal Year: 2023, Volume and Issue: 112(4), P. 676 - 686.e4

Published: Dec. 13, 2023

In early Alzheimer's disease (AD) β-amyloid (Aβ) deposits throughout association cortex and tau appears in the entorhinal (EC). Why these initially appear disparate locations is not understood. Using task-based fMRI multimodal PET imaging, we assess impact of local AD pathology on network-to-network interactions. We show that pathologies flip interactions between default mode network (DMN) medial temporal lobe (MTL) from inhibitory to excitatory. The DMN hyperexcited with increasing levels Aβ, which drives hyperexcitability within MTL this directed hyperexcitation by predicts rate accumulation EC. Our results support a model whereby Aβ induces disruptions excitatory-inhibitory balance DMN, driving MTL, leading accumulation. propose Aβ-induced candidate causal route remote EC-tau

Language: Английский

Citations

47
Epilepsy and epileptiform activity in late-onset Alzheimer disease: clinical and pathophysiological advances, gaps and conundrums DOI
Anita Kamondi, Madeleine Grigg‐Damberger, Wolfgang Löscher

et al.

Nature Reviews Neurology, Journal Year: 2024, Volume and Issue: 20(3), P. 162 - 182

Published: Feb. 14, 2024

Language: Английский

Citations

33
DecGAN: Decoupling Generative Adversarial Network for Detecting Abnormal Neural Circuits in Alzheimer’s Disease DOI
Junren Pan, Qiankun Zuo, Bing-Chuan Wang

et al.

IEEE Transactions on Artificial Intelligence, Journal Year: 2024, Volume and Issue: 5(10), P. 5050 - 5063

Published: June 18, 2024

Language: Английский

Citations

18
Amyloid-β: a potential link between epilepsy and cognitive decline DOI
Michele Romoli, Arjune Sen, Lucilla Parnetti

et al.

Nature Reviews Neurology, Journal Year: 2021, Volume and Issue: 17(8), P. 469 - 485

Published: June 11, 2021

Language: Английский

Citations

98