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Sensory gamma entrainment: Impact on amyloid protein and therapeutic mechanism

BRAIN RESEARCH BULLETIN (2023)

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Auditory or Audiovisual Stimulation Ameliorates Cognitive Impairment and Neuropathology in ApoE4 Knock-In Mice

Harry Jung et al.

Summary: This study conducted an experiment with a mouse model of Alzheimer's disease, and found that auditory stimulation could slow down the progression of the disease, while audiovisual stimulation had additional effects through multisensory integration. The mice in the auditory and audiovisual stimulation groups showed better performance in behavioral tests and lower levels of amyloid-beta and apoptotic cell death in their brain tissues. These findings provide new insights for the treatment of early-stage Alzheimer's disease.

INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES (2023)

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Article Geriatrics & Gerontology

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

Yang Liu et al.

Summary: This study aims to explore the safety and effectiveness of combining transcranial alternating current stimulation (tACS) with sound stimulation for cognitive improvement in mild to moderate Alzheimer's disease (AD) patients. 87 patients will be randomly divided into three groups to receive standardized treatment regimens, and the changes in Alzheimer's Disease Assessment Scale-Cognitive (ADAS-Cog) scores and brain networks will be evaluated. The study may provide insights into the potential mechanism of tACS combined with sound stimulation in treating AD patients.

FRONTIERS IN AGING NEUROSCIENCE (2023)

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Article Neurosciences

Forty-hertz light stimulation does not entrain native gamma oscillations in Alzheimer's disease model mice

Marisol Soula et al.

Summary: The authors find that 40-Hz flickering light does not suppress A beta, activate microglia or engage native gamma oscillations. Thus, visual flicker stimulation may not be a viable mechanism for altering AD pathology and modulating deep structures.

NATURE NEUROSCIENCE (2023)

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Article Geriatrics & Gerontology

Alterations in theta-gamma coupling and sharp wave-ripple, signs of prodromal hippocampal network impairment in the TgF344-AD rat model

Monica van den Berg et al.

Summary: Alzheimer's disease is a severe neurodegenerative disorder caused by the accumulation of toxic proteins. This study suggests that targeting early synaptic dysfunction could be a potential therapeutic approach for this disease.

FRONTIERS IN AGING NEUROSCIENCE (2023)

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Review Behavioral Sciences

Gamma sensory entrainment for cognitive improvement in neurodegenerative diseases: opportunities and challenges ahead

Prangya Parimita Sahu et al.

Summary: Neural oscillations are categorized into different frequency bands associated with cognitive functions, with the gamma band playing a significant role. Decreased gamma oscillation is linked to cognitive declines in diseases like Alzheimer's, but studies have discovered that inducing gamma oscillations through sensory stimulation can improve cognition in AD patients and mouse models. This review examines the use of sensory stimulation as a therapeutic strategy in AD and discusses future opportunities and challenges in using this approach for other neurodegenerative and neuropsychiatric diseases.

FRONTIERS IN INTEGRATIVE NEUROSCIENCE (2023)

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Article Biology

Moderate white light exposure enhanced spatial memory retrieval by activating a central amygdala-involved circuit in mice

MengJuan Shang et al.

Summary: A white light exposure scheme activates amygdala circuitry and enhances spatial memory retrieval in mice. Short-term exposure to moderate white light during Y-maze test promotes spatial memory retrieval and induces mild anxiety in mice. The activation of a circuit including neurons in the central amygdala, locus coeruleus, and dentate gyrus is involved in this beneficial effect.

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Dysfunction of the blood-brain barrier in Alzheimer's disease: Evidence from human studies

Carolin Kurz et al.

Summary: The pathological processes leading to synapse loss, neuronal loss, brain atrophy and gliosis in Alzheimer's disease (AD) are not fully understood. This review focuses on the clinical correlations and pathophysiological concepts of blood-brain barrier (BBB) damage in AD. Specific changes in intercellular structures, reduced expression of transendothelial carriers, and activation of astroglia and monocytes/macrophages characterize BBB damage in AD. Magnetic resonance imaging shows early BBB dysfunction in AD-specific brain regions. Novel therapeutic approaches aim to open the BBB and improve drainage of amyloid-beta (A beta) from the brain.

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Gamma frequency light flicker regulates amyloid precursor protein trafficking for reducing β-amyloid load in Alzheimer's disease model

Qi Shen et al.

Summary: The study found that inducing gamma oscillations with non-invasive light flicker can reduce Alzheimer's disease-related pathology. By increasing the anchoring of amyloid precursor protein (APP) to the plasma membrane for non-amyloidogenic processing and interacting with KCC2, it helps maintain surface GABA(A) receptor alpha 1 levels and reduce beta-amyloid (A beta) production. These findings highlight the importance of enhancing APP trafficking to the plasma membrane in the reduction of A beta load in Alzheimer's disease.

AGING CELL (2022)

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Behavior of olfactory-related frontal lobe oscillations in Alzheimer's disease and MCI: A pilot study

Seyyedeh Nahaleh Fatemi et al.

Summary: This pilot study examines the phase amplitude coupling and synchronization of slow-gamma and theta oscillations in the context of memory retrieval and cognitive functions. The findings reveal significant differences between healthy individuals and patients with amnestic Mild Cognitive Impairment (aMCI) and Alzheimer's Disease (AD), providing insights into the underlying processes in these cognitive disorders. The study also proposes a diagnostic method for aMCI based on comparing brain responses during olfactory stimulation and rest.

INTERNATIONAL JOURNAL OF PSYCHOPHYSIOLOGY (2022)

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Article Physiology

Combined effects of aerobic exercise and 40-Hz light flicker exposure on early cognitive impairments in Alzheimer's disease of 3xTg mice

Sang-Seo Park et al.

Summary: Exercising in a 40-Hz light flicker environment was found to be more effective than exercise or 40-Hz light flicker alone. This synergistic effect may prevent cognitive dysfunction by inhibiting the Aβ, tau pathway, and neuroinflammation, and enhancing neuroplasticity and mitochondrial functions in the hippocampus during the early stages of Alzheimer's disease.

JOURNAL OF APPLIED PHYSIOLOGY (2022)

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Prominent gamma band activity during visual motion perception in early-stage Alzheimer's disease

Nobushige Naito et al.

Summary: This study investigated induced gamma band activity during visual motion perception in early stage Alzheimer's disease (AD) patients and found that AD patients had significantly higher power of induced gamma band activities, which was associated with better cognitive performance in terms of attention and concentration.

PLOS ONE (2022)

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THE LONG ROAD TO A CURE FOR ALZHEIMER'S DISEASE IS PAVED WITH FAILURES

Sofia Moutinho

NATURE MEDICINE (2022)

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Decreased Frontal Gamma Activity in Alzheimer Disease Patients

Elias P. Casula et al.

Summary: This study investigates the oscillatory activity in Alzheimer's disease patients using a novel method combining transcranial magnetic stimulation and electroencephalography. The results show a significant reduction of frontal gamma activity in Alzheimer's disease patients, which is associated with impaired cortical plasticity and cognitive decline.

ANNALS OF NEUROLOGY (2022)

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Gamma frequency sensory stimulation in mild probable Alzheimer's dementia patients: Results of feasibility and pilot studies

Diane Chan et al.

Summary: Non-invasive Gamma ENtrainment Using Sensory stimulation (GENUS) at 40Hz reduces Alzheimer's disease pathology and improves behavioral testing performance in mouse models of AD.

PLOS ONE (2022)

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Review Geriatrics & Gerontology

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

Valerio Manippa et al.

Summary: This review summarizes the evidence on the effectiveness of Gamma Entrainment Using Sensory stimulation (GENUS) for the treatment of Alzheimer's disease (AD), and emphasizes the need for further research.

FRONTIERS IN AGING NEUROSCIENCE (2022)

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The role of gamma oscillations in central nervous system diseases: Mechanism and treatment

Ao Guan et al.

Summary: Gamma oscillations are rhythmic electric processes of neuron groups in the brain, crucial for perception, movement, memory, and emotion. Abnormal gamma oscillations are associated with central nervous system diseases, while GENUS can provide significant neuroprotection.

FRONTIERS IN CELLULAR NEUROSCIENCE (2022)

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Alterations in a cross-hemispheric circuit associates with novelty discrimination deficits in mouse models of neurodegeneration

Chinnakkaruppan Adaikkan et al.

Summary: A reduction in white matter and correlated activity is observed in neurodegenerative diseases, but the underlying mechanisms and cognitive relevance are unclear. This study reveals a novel circuit connecting the two cerebral hemispheres in the visual cortex, which plays a role in novelty discrimination behavior. Impairment of this circuit is observed in mouse models of neurodegeneration.

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Yeseung Park et al.

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Long-term gamma transcranial alternating current stimulation improves the memory function of mice with Alzheimer's disease

Linyan Wu et al.

Summary: The study found that long-term gamma-frequency tACS can reduce Aβ levels, increase gamma oscillation power, and ultimately improve short-term memory function in an AD mouse model. In comparison, the short-term tACS treatment showed less significant effects.

FRONTIERS IN AGING NEUROSCIENCE (2022)

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Mutual Interactions between Brain States and Alzheimer's Disease Pathology: A Focus on Gamma and Slow Oscillations

Nicole Byron et al.

Summary: Electrical activity in the brain changes dynamically throughout the day, and abnormal brain activity is associated with various brain disorders. Controlling brain activity can modify disease pathologies and cognitive functions. Abnormalities in brain state have been recognized as biomarkers of brain diseases, and manipulating brain state can potentially modify disease pathology.

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A Visual Circuit Related to the Nucleus Reuniens for the Spatial-Memory-Promoting Effects of Light Treatment

Xiaodan Huang et al.

Summary: Exposure to bright-light treatment promotes spatial memory through a di-synaptic visual circuit involving specific retinal ganglion cells and thalamic neurons, with the effects dependent on the activation of these pathways.

NEURON (2021)

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Kenjiro Ono et al.

Summary: Alzheimer's disease is a common age-related neurodegenerative disorder characterized by plaques composed of amyloid beta-protein and neurofibrillary tangles of tau protein in the brain. Genetic studies have suggested that the misfolding and aggregation of Aβ molecules play a critical role in the pathogenesis of AD. Recent combination studies using NMR and cryo-EM have provided detailed information on the aggregation process and structural polymorphism of Aβ fibrils.

NEUROCHEMISTRY INTERNATIONAL (2021)

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Alzheimer's disease

Philip Scheltens et al.

Summary: Alzheimer's disease is projected to see a significant increase in prevalence in the future, with genetics playing a key role. Novel biomarkers and lifestyle-based prevention trials show promising therapeutic potential. Promising pharmacological treatments are advancing in clinical trials, targeting amyloid beta, tau, and inflammation.

LANCET (2021)

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Enhancing GABAergic signaling ameliorates aberrant gamma oscillations of olfactory bulb in AD mouse models

Ming Chen et al.

Summary: The study revealed an increase in gamma oscillations in the olfactory bulb before plaque formation in AD models, along with altered olfactory behavior. This was associated with decreased excitatory responses of M/T cells, reduced GABA release ability, and compensatory increases in GABA(A)R subunit levels. The GABA uptake inhibitor tiagabine showed potential as a therapeutic strategy for early AD symptoms.

MOLECULAR NEURODEGENERATION (2021)

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Histone Deacetylase Inhibitor Improves the Dysfunction of Hippocampal Gamma Oscillations and Fast Spiking Interneurons in Alzheimer's Disease Model Mice

Keiko Takasu et al.

Summary: This study revealed that histone acetylation regulates hippocampal gamma oscillations by modulating the activity of fast spiking interneurons, and the deficits in gamma oscillations in AD model mice can be restored by HDAC inhibitor or NR4a activator. These findings suggest a potential therapeutic target for treating cognitive impairment in AD patients.

FRONTIERS IN MOLECULAR NEUROSCIENCE (2021)

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Somatosensory dysfunction is masked by variable cognitive deficits across patients on the Alzheimer's disease spectrum

Alex Wiesman et al.

Summary: This study found that differences in somatosensory function in patients with AD were largely non-significant until cognitive variability was taken into account. Once attention and processing speed abilities were considered, robust differences emerged in gamma-frequency somatosensory response amplitude and gating, suggesting insults to functional somatosensory processing in primary sensory cortices in patients with AD.

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Effects of transcranial ultrasound stimulation pulsed at 40 Hz on Aβ plaques and brain rhythms in 5xFAD mice

Mincheol Park et al.

Summary: The study showed that ultrasound stimulation can reduce A beta load in the brain of an AD mouse model and improve brain connectivity. Levels of A beta 42, especially insoluble A beta 42, were decreased in the pre- and infra-limbic cortex in the treatment group, and a reduction in the number of A beta plaques was observed.

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Sensory-Evoked 40-Hz Gamma Oscillation Improves Sleep and Daily Living Activities in Alzheimer's Disease Patients

Aylin Cimenser et al.

Summary: The study found that 40 Hz sensory stimulation therapy can benefit AD patients by reducing nighttime activity and maintaining functional abilities.

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Optimal flickering light stimulation for entraining gamma waves in the human brain

Kanghee Lee et al.

Summary: Through studying the optimal way of entraining gamma waves with flickering light stimulus in young adults, it was found that red light was the most effective, followed by white light; lights with higher luminance intensities (700 and 400cd/m²) entrained stronger gamma waves than those with lower luminance intensities (100 and 10cd/m²); lights flickering at 34-38 Hz entrained stronger and more widespread gamma waves than those flickering at 40-50 Hz.

SCIENTIFIC REPORTS (2021)

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Visuospatial alpha and gamma oscillations scale with the severity of cognitive dysfunction in patients on the Alzheimer's disease spectrum

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Gamma Entrainment: Impact on Neurocircuits, Glia, and Therapeutic Opportunities

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Physical exercise during exposure to 40-Hz light flicker improves cognitive functions in the 3xTg mouse model of Alzheimer's disease

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Non-invasive 40-Hz Light Flicker Ameliorates Alzheimer's-Associated Rhythm Disorder via Regulating Central Circadian Clock in Mice

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Transcranial focused ultrasound, pulsed at 40 Hz, activates microglia acutely and reduces Aβ load chronically, as demonstrated in vivo

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Review Biochemistry & Molecular Biology

The amyloid precursor protein and postnatal neurogenesis/neuroregeneration

YN Chen et al.

BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS (2006)

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Review Biochemistry & Molecular Biology

Oxidative stress and autophagy

R Kiffin et al.

ANTIOXIDANTS & REDOX SIGNALING (2006)

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Article Neurosciences

Synaptic activity regulates interstitial fluid amyloid-β levels in vivo

JR Cirrito et al.

NEURON (2005)

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Article Neurosciences

Microglial activation facilitates Aβ plaque removal following intracranial anti-Aβ antibody administration

DM Wilcock et al.

NEUROBIOLOGY OF DISEASE (2004)

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Article Biochemistry & Molecular Biology

The low density lipoprotein receptor-related protein 1B retains β-amyloid precursor protein at the cell surface and reduces amyloid-β peptide production

JA Cam et al.

JOURNAL OF BIOLOGICAL CHEMISTRY (2004)

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Article Biochemistry & Molecular Biology

Systemic catabolism of Alzheimer's Aβ40 and Aβ42

J Ghiso et al.

JOURNAL OF BIOLOGICAL CHEMISTRY (2004)

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Review Neurosciences

Roles of amyloid precursor protein and its fragments in regulating neural activity, plasticity and memory

PR Turner et al.

PROGRESS IN NEUROBIOLOGY (2003)

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Review Multidisciplinary Sciences

Medicine - The amyloid hypothesis of Alzheimer's disease: Progress and problems on the road to therapeutics

J Hardy et al.

SCIENCE (2002)

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Letter Biochemistry & Molecular Biology

Clearance of amyloid β-peptide from brain:: transport or metabolism?

BV Zlokovic et al.

NATURE MEDICINE (2000)

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