Gamma Oscillations in Alzheimer’s Disease and Their Potential Therapeutic Role DOI
Artemis Traikapi, Nikos Konstantinou

Frontiers in Systems Neuroscience, Journal Year: 2021, Volume and Issue: 15

Published: Dec. 13, 2021

Despite decades of research, Alzheimer’s Disease (AD) remains a lethal neurodegenerative disorder for which there are no effective treatments. This review examines the latest evidence novel and newly introduced perspective, focuses on restoration gamma oscillations investigates their potential role in treatment AD. Gamma brain activity (∼25–100 Hz) has been well-known its cognitive function, including memory, it is fundamental healthy intra-brain communication. Aberrant have observed both mice AD models human patients. A recent line work demonstrated that entrainment, through auditory visual sensory stimulation, can effectively attenuate pathology improve function disease. The first from patients indicate entrainment therapy reduce loss functional connectivity atrophy, ameliorate several pathological markers Even though research still infancy, suggests gamma-based may disease-modifying effect signified new promising era research.

Language: Английский

New Insights Into the Pathogenesis of Alzheimer's Disease DOI Creative Commons
Liyuan Fan, Chengyuan Mao, Xinchao Hu

et al.

Frontiers in Neurology, Journal Year: 2020, Volume and Issue: 10

Published: Jan. 10, 2020

Alzheimer's disease (AD), a common neurodegenerative in the elderly and most prevalent cause of dementia, is characterized by progressive cognitive impairment. The prevalence AD continues to increase worldwide, becoming great healthcare challenge twenty-first century. In more than 110 years since was discovered, many related pathogenic mechanisms have been proposed, recognized hypotheses are amyloid tau hypotheses. However, almost all clinical trials targeting these not identified any effective methods treat AD. Scientists gradually moving away from simple assumption, as proposed original hypothesis, new theories pathogenesis, including gamma oscillations, prion transmission, cerebral vasoconstriction, growth hormone secretagogue receptor 1α (GHSR1α)-mediated mechanism, infection. To place findings context, we first reviewed neuropathology further discussed insights pathogenesis

Language: Английский

Citations

289
Gamma Entrainment: Impact on Neurocircuits, Glia, and Therapeutic Opportunities DOI
Chinnakkaruppan Adaikkan, Li‐Huei Tsai

Trends in Neurosciences, Journal Year: 2019, Volume and Issue: 43(1), P. 24 - 41

Published: Dec. 10, 2019

Language: Английский

Citations

181
GABAergic Inhibitory Interneuron Deficits in Alzheimer’s Disease: Implications for Treatment DOI Creative Commons

Yilan Xu,

Man-Na Zhao,

Yuying Han

et al.

Frontiers in Neuroscience, Journal Year: 2020, Volume and Issue: 14

Published: June 30, 2020

Alzheimer's disease (AD) is a neurodegenerative disorder characterized clinically by severe cognitive deficits and pathologically amyloid plaques, neuronal loss, neurofibrillary tangles. Abnormal β-protein (Aβ) deposition in the brain often thought of as major initiating factor AD neuropathology. However, gamma-aminobutyric acid (GABA) inhibitory interneurons are resistant to Aβ deposition, decreases synaptic glutamatergic transmission decrease neural network activity. Furthermore, there now evidence suggesting that activity aberrantly increased patients animal models due functional decreased GABA interneurons, contributing deficits. Here we describe roles played excitatory neurons Aβ-induced how altered regulate We also comprehensively review recent studies on receptors can be exploited for therapeutic benefit. an emerging target AD, with further clinical trials urgently warranted.

Language: Английский

Citations

154
The Locus Coeruleus- Norepinephrine System in Stress and Arousal: Unraveling Historical, Current, and Future Perspectives DOI Creative Commons
Jennifer A. Ross, Elisabeth J. Van Bockstaele

Frontiers in Psychiatry, Journal Year: 2021, Volume and Issue: 11

Published: Jan. 27, 2021

Arousal may be understood on a spectrum, with excessive sleepiness, cognitive dysfunction, and inattention one side, wakeful state in the middle, hypervigilance, panic, psychosis other side. However, historically, concepts of arousal stress have been challenging to define as measurable experimental variables. Divergent efforts study these subjects given rise several disciplines, including neurobiology, neuroendocrinology, neuroscience. We discuss technological advancements that chronologically led our current understanding system, focusing multifaceted nucleus locus coeruleus. share contemporary perspective hypotheses others context capabilities future developments will required move forward this area research.

Language: Английский

Citations

144
Tipping the Scales: Peptide-Dependent Dysregulation of Neural Circuit Dynamics in Alzheimer’s Disease DOI Creative Commons
Sam Harris, Fred Wolf, Bart De Strooper

et al.

Neuron, Journal Year: 2020, Volume and Issue: 107(3), P. 417 - 435

Published: June 23, 2020

Language: Английский

Citations

139
Microglia regulate synaptic development and plasticity DOI Creative Commons

Megumi Andoh,

Ryuta Koyama

Developmental Neurobiology, Journal Year: 2021, Volume and Issue: 81(5), P. 568 - 590

Published: Feb. 14, 2021

Synapses are fundamental structures of neural circuits that transmit information between neurons. Thus, the process circuit formation via proper synaptic connections shapes basis brain functions and animal behavior. continuously undergo repeated elimination throughout lifetime an organism, reflecting dynamics function. The structural transformation synapses has been described mainly in relation to activity-dependent strengthening weakening functions, is, functional plasticity synapses. An increasing number studies have unveiled roles microglia, brain-resident immune cells survey parenchyma with highly motile processes, synapse as well regulating Over past 15 years, molecular mechanisms underlying microglia-dependent regulation thoroughly studied, researchers reported disruption causes dysfunction leads diseases. In this review, we will broadly introduce report microglia possible mechanisms.

Language: Английский

Citations

124
Gamma frequency sensory stimulation in mild probable Alzheimer’s dementia patients: Results of feasibility and pilot studies DOI Creative Commons
Diane Chan,

Ho‐Jun Suk,

Brennan Jackson

et al.

PLoS ONE, Journal Year: 2022, Volume and Issue: 17(12), P. e0278412 - e0278412

Published: Dec. 1, 2022

Non-invasive Gamma ENtrainment Using Sensory stimulation (GENUS) at 40Hz reduces Alzheimer's disease (AD) pathology such as amyloid and tau levels, prevents cerebral atrophy, improves behavioral testing performance in mouse models of AD. Here, we report data from (1) a Phase 1 feasibility study (NCT04042922, ClinicalTrials.gov) cognitively normal volunteers (n = 25), patients with mild AD dementia 16), epilepsy who underwent intracranial electrode monitoring 2) to assess safety single brief GENUS session induce entrainment (2) single-blinded, randomized, placebo-controlled 2A pilot (NCT04055376) probable 15) safety, compliance, entrainment, exploratory clinical outcomes after chronic daily sensory for 3 months. Our showed that was safe effectively induced both cortical regions other subcortical structures the hippocampus, amygdala, insula, gyrus rectus. demonstrated light sound well-tolerated compliance equally high control active groups, participants inaccurate guessing their group assignments prior unblinding. Electroencephalography recordings show our device safely dementia. After months stimulation, receiving (i) lesser ventricular dilation hippocampal (ii) increased functional connectivity default mode network well medial visual network, (iii) better on face-name association delayed recall test, (iv) improved measures activity rhythmicity compared group. These results support further evaluation pivotal trial evaluate its potential novel disease-modifying therapeutic

Language: Английский

Citations

116
Exposure to gamma tACS in Alzheimer’s disease: A randomized, double-blind, sham-controlled, crossover, pilot study DOI Creative Commons
Alberto Benussi, Valentina Cantoni, Maria Sofia Cotelli

et al.

Brain stimulation, Journal Year: 2021, Volume and Issue: 14(3), P. 531 - 540

Published: March 21, 2021

To assess whether exposure to non-invasive brain stimulation with transcranial alternating current at γ frequency (γ-tACS) applied over Pz (an area overlying the medial parietal cortex and precuneus) can improve memory modulate cholinergic transmission in mild cognitive impairment due Alzheimer's disease (MCI-AD).In this randomized, double-blind, sham controlled, crossover pilot study, participants were assigned a single 60 min treatment γ-tACS or tACS. Each subject underwent clinical evaluation including assessment of episodic pre- post-γ-tACS stimulation. Indirect measures evaluated using magnetic (TMS) tACS evaluated.Twenty MCI-AD completed study. No tACS-related side effects observed, intervention was well tolerated all participants. We observed significant improvement Rey auditory verbal learning (RAVL) test total recall (5.7 [95% CI, 4.0 7.4], p < 0.001) long delayed scores (1.3 0.4 2.1], = 0.007) after but not Face-name associations improved during (4.3 2.8 5.8], Short latency afferent inhibition, an indirect measure TMS, increased only (0.31 0.24 0.38], tACS.exposure showed performances, along restoration intracortical connectivity neurotransmission, compared

Language: Английский

Citations

108
Forty-hertz light stimulation does not entrain native gamma oscillations in Alzheimer’s disease model mice DOI
Marisol Soula, Alejandro Martín‐Ávila, Yiyao Zhang

et al.

Nature Neuroscience, Journal Year: 2023, Volume and Issue: 26(4), P. 570 - 578

Published: March 6, 2023

Language: Английский

Citations

103
Multisensory gamma stimulation promotes glymphatic clearance of amyloid DOI Creative Commons
Mitchell H. Murdock,

Cheng-Yi Yang,

Na Sun

et al.

Nature, Journal Year: 2024, Volume and Issue: 627(8002), P. 149 - 156

Published: Feb. 28, 2024

Abstract The glymphatic movement of fluid through the brain removes metabolic waste 1–4 . Noninvasive 40 Hz stimulation promotes neural activity in multiple regions and attenuates pathology mouse models Alzheimer’s disease 5–8 Here we show that multisensory gamma influx cerebrospinal efflux interstitial cortex 5XFAD model disease. Influx was associated with increased aquaporin-4 polarization along astrocytic endfeet dilated meningeal lymphatic vessels. Inhibiting clearance abolished removal amyloid by stimulation. Using chemogenetic manipulation a genetically encoded sensor for neuropeptide signalling, found vasoactive intestinal peptide interneurons facilitate regulating arterial pulsatility. Our findings establish novel mechanisms recruit system to remove amyloid.

Language: Английский

Citations

93