Alzheimer’s disease as a synaptopathy: Evidence for dysfunction of synapses during disease progression

Frontiers in Synaptic Neuroscience, Год журнала: 2023, Номер 15

Опубликована: Март 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.

Язык: Английский

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The impact of gamma transcranial alternating current stimulation (tACS) on cognitive and memory processes in patients with mild cognitive impairment or Alzheimer's disease: A literature review

Brain stimulation, Год журнала: 2023, Номер 16(3), С. 748 - 755

Опубликована: Апрель 5, 2023

Highlights•40 Hz tACS enhances gamma oscillations and memory performance in MCI/AD patients.•Active 40 increases spectral power patients over sham.•Gamma stimulation may aid clearance of tau mouse models AD patients.AbstractBackgroundTranscranial alternating current (tACS)—a noninvasive brain technique that modulates cortical through entrainment—has been demonstrated to alter oscillatory activity enhance cognition healthy adults. TACS is being explored as a tool improve patient populations with mild cognitive impairment (MCI) Alzheimer's disease (AD).ObjectiveTo review the growing body literature findings obtained from application MCI or AD, highlighting effects on function, memory, cognition. Evidence use animal also discussed. Important parameters are underscored for consideration protocols aim apply therapeutic MCI/AD.FindingsThe has shown promising results improvement processes impacted MCI/AD. These data demonstrate potential an interventional stand-alone alongside pharmacological and/or other behavioral interventions MCI/AD.ConclusionsWhile evidenced encouraging results, this function pathophysiology remains be fully determined. This explores highlights need continued research course by reinstating activity, improving processing, delaying progression, remediating abilities

Язык: Английский

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An update on the use of gamma (multi)sensory stimulation for Alzheimer’s disease treatment

Frontiers in Aging Neuroscience, Год журнала: 2022, Номер 14

Опубликована: Дек. 15, 2022

Alzheimer's disease (AD) is characterized by reduced fast brain oscillations in the gamma band (γ, > 30 Hz). Several animal studies show that inducing through (multi)sensory stimulation at 40 Hz has potential to impact AD-related cognitive decline and neuropathological processes, including amyloid plaques deposition, neurofibrillary tangles formation, neuronal synaptic loss. Therefore Gamma Entrainment Using Sensory (GENUS) among most promising approaches for AD patients' treatment. This review summarizes evidence on GENUS effectiveness, from models patients. Despite application human its infancy, available findings suggest feasibility treatment of AD. We discuss such results light parameter improvement possible underlying mechanisms. finally emphasize need further research development as a disease-modifying non-pharmacological intervention.

Язык: Английский

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Audiovisual gamma stimulation for the treatment of neurodegeneration

Journal of Internal Medicine, Год журнала: 2023, Номер 295(2), С. 146 - 170

Опубликована: Дек. 19, 2023

Alzheimer's disease (AD) is the most common type of neurodegenerative and a health challenge with major social economic consequences. In this review, we discuss therapeutic potential gamma stimulation in treating AD delve into possible mechanisms responsible for its positive effects. Recent studies reveal that it feasible safe to induce 40 Hz brain activity patients through range multisensory noninvasive electrical or magnetic methods. Although research clinical these interventions still nascent stages, suggest can yield beneficial effects on function, pathology, cognitive function individuals AD. Specifically, involving light, auditory, vibrotactile stimulation, as well techniques such transcranial alternating current stimulation. The precise underpinning are not yet fully elucidated, but preclinical have provided relevant insights. We evidence related both neuronal nonneuronal may be involved, touching upon relevance interneurons, neuropeptides, specific synaptic translating widespread within brain. also explore roles microglia, astrocytes, vasculature mediating function. Lastly, examine upcoming trials contemplate future applications management disorders.

Язык: Английский

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Alzheimer’s disease: a review on the current trends of the effective diagnosis and therapeutics

Frontiers in Aging Neuroscience, Год журнала: 2024, Номер 16

Опубликована: Авг. 9, 2024

The most prevalent cause of dementia is Alzheimer's disease. Cognitive decline and accelerating memory loss characterize it. disease advances sequentially, starting with preclinical stages, followed by mild cognitive and/or behavioral impairment, ultimately leading to dementia. In recent years, healthcare providers have been advised make an earlier diagnosis Alzheimer's, prior individuals developing Regrettably, the identification early-stage in clinical settings can be arduous due tendency patients disregard symptoms as typical signs aging. Therefore, accurate prompt essential order facilitate development disease-modifying secondary preventive therapies onset symptoms. There has a notable shift goal process, transitioning from merely confirming presence symptomatic AD recognizing illness its early, asymptomatic phases. Understanding evolution putting effective diagnostic therapeutic management into practice requires understanding this concept. outcomes study will enhance in-depth knowledge current status disease's treatment, justifying necessity for quest potential novel biomarkers that contribute determining stage disease, particularly earliest stages. Interestingly, latest trial on pharmacological agents, nonpharmacological treatments such behavior modification, exercise, training well alternative approach phytochemicals neuroprotective agents covered detailed.

Язык: Английский

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The emerging field of non-invasive brain stimulation in Alzheimer’s disease

Brain, Год журнала: 2024, Номер unknown

Опубликована: Ноя. 20, 2024

Abstract Treating cognitive impairment is a holy grail of modern clinical neuroscience. In the past few years, non-invasive brain stimulation increasingly emerging as therapeutic approach to ameliorate performance in patients with and an augmentation persons whose within normal limits. Alzheimer’s disease, better understanding connectivity function has allowed for development different protocols. Recent studies have shown that transcranial methods enhancing plasticity several modalities beneficial effects on functions. Amelioration been preclinical behaviour transgenic mouse models pathology variable severity impairment. While field still grappling issues related standardization target population, frequency, intensity, treatment duration stimulated region, positive outcomes reported functions markers pathology. Here we review most encouraging protocols based repetitive magnetic stimulation, direct current alternating visual-auditory photobiomodulation focused ultrasound, which demonstrated efficacy enhance or slow decline disease. Beneficial are associated modulation specific networks. The promising results obtained targeting key hubs higher-level networks, such frontal-parietal network default mode network. personalization parameters according individual features sheds new light optimizing future applications.

Язык: Английский

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Targeting Neural Oscillations for Cognitive Enhancement in Alzheimer’s Disease

Medicina, Год журнала: 2025, Номер 61(3), С. 547 - 547

Опубликована: Март 20, 2025

Alzheimer’s disease (AD), the most prevalent form of dementia, is marked by progressive cognitive decline, affecting memory, language, orientation, and behavior. Pathological hallmarks include extracellular amyloid plaques intracellular tau tangles, which disrupt synaptic function connectivity. Neural oscillations, rhythmic synchronization neuronal activity across frequency bands, are integral to processes but become dysregulated in AD, contributing network dysfunction memory impairments. Targeting these oscillations has emerged as a promising therapeutic strategy. Preclinical studies have demonstrated that specific modulations can restore oscillatory balance, improve plasticity, reduce pathology. In animal models, interventions, such gamma entrainment using sensory stimulation transcranial alternating current (tACS), shown efficacy enhancing modulating neuroinflammatory responses. Clinical trials reported improvements with repetitive magnetic (rTMS) deep brain (DBS), particularly when targeting key hubs memory-related networks, default mode (DMN) frontal–parietal network. Moreover, gamma-tACS been linked increased cholinergic enhanced connectivity, correlated improved outcomes AD patients. Despite advancements, challenges remain optimizing parameters, individualizing treatment protocols, understanding long-term effects. Emerging approaches, including pulse (TPS) closed-loop adaptive neuromodulation, hold promise for refining strategies. Integrating neuromodulation pharmacological lifestyle interventions may maximize benefits. Continued interdisciplinary efforts essential refine approaches translate them into clinical practice, advancing potential neural oscillation-based therapies AD.

Язык: Английский

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Transcranial alternating current stimulation combined with sound stimulation improves cognitive function in patients with Alzheimer’s disease: Study protocol for a randomized controlled trial

Frontiers in Aging Neuroscience, Год журнала: 2023, Номер 14

Опубликована: Янв. 9, 2023

Background The number of patients with Alzheimer’s disease (AD) worldwide is increasing yearly, but the existing treatment methods have poor efficacy. Transcranial alternating current stimulation (tACS) a new for AD, offline effect tACS insufficient. To prolong effect, we designed to combine sound maintain long-term post-effect. Materials and explore safety effectiveness combined its impact on cognition AD patients. This trial will recruit 87 mild moderate AD. All were randomly divided into three groups. change in Disease Assessment Scale-Cognitive (ADAS-Cog) scores from day before end 3 months after was used as main evaluation index. We also changes brain structural network, functional metabolic network each group treatment. Discussion hope conclude that safe tolerable under standardized regimens. Compared alone or alone, combination had significant cognitive improvement. screen out better plan previously unexplored, non-invasive joint intervention improve patients’ status. study may identify potential mechanism treating Clinical Trial Registration Clinicaltrials.gov , NCT05251649. Registered February 22, 2022.

Язык: Английский

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A Focused Review of Gamma Neuromodulation as a Therapeutic Target in Alzheimer’s Spectrum Disorders

Journal of Psychiatry and Brain Science, Год журнала: 2024, Номер unknown

Опубликована: Янв. 1, 2024

The aging population of the world is increasing at an unprecedented rate which expected to lead a corresponding unparalleled increase in age related diseases. Of particular concern are large number older adults develop Alzheimer's disease (AD), will require extraordinary local, national and worldwide healthcare resources. In this context, innovative interventions needed urgently delay AD onset thereby give our systems time prepare provide meaningful care populations. This focused review discusses crucial role frontal gamma oscillations as therapeutic target or ameliorate cognitive decline AD. Frontal oscillations, including from prefrontal cortical areas, serve biomarker for working memory other functions, their impairment observed before clinical symptoms manifest. evaluates evidence animal models human subjects highlight correlation between wave abnormalities deterioration. Furthermore, summarizes 11 studies using neuromodulation techniques designed stimulate mild (MCI) patients, transcranial electrical stimulation, magnetic rhythmic sensory stimulation. These have shown promise mitigating early-stage decline, evidenced by improved performance on tests, increased oscillatory responses, some even reduced brain atrophy. early suggest that treatments strengthen responses through promising approach may adjunct therapies standalone treatment

Язык: Английский

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Parvalbumin interneuron cell-to-network plasticity: mechanisms and therapeutic avenues

Trends in Pharmacological Sciences, Год журнала: 2024, Номер 45(7), С. 586 - 601

Опубликована: Май 18, 2024

Alzheimer's disease (AD) and schizophrenia (SCZ) represent two major neuropathological conditions with a high burden. Despite their distinct etiologies, patients suffering from AD or SCZ share common burden of disrupted memory functions unattended by current therapies. Recent preclinical analyses highlight cell-type-specific contributions parvalbumin interneurons (PVIs), particularly the plasticity cellular excitability, towards intact neuronal network function (cell-to-network plasticity) performance. Here we argue that deficits PVI cell-to-network may underlie in SCZ, explore therapeutic avenues: targeting PVI-specific neuromodulation, including neuropeptides, recruitment synchrony gamma frequency range (40 Hz) external stimulation. We finally propose these approaches be merged under consideration recent insights into human brain physiology.

Язык: Английский

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