Summary: A new collection of articles explores mapping brain overexcitability that underpins the dysregulation of vigilance, sleep-wake cycles, and validating effective biomarkers for Alzheimer’s disease.

Source: IOS Press

Neurophysiological techniques (e.g., electroencephalography, EEG, transcranial magnetic stimulation, TMS) allow an informed investigation of the brain overexcitability underpinning the typical difficulty of maintaining a stable level of vigilance or experiencing a regular sleep-wake cycle in patients living with Alzheimer’s disease (AD).

Importantly, this difficulty has a significant impact on the level of consciousness of patients, affecting patients’ ability to follow TV programs and social conversation during the daytime and preventing a deep sleep at night.

As an important advantage, neurophysiological techniques can be applied in preclinical and clinical research models of the disease, its progression, and the effects of pharmacological and non-pharmacological interventions.

special Mini-Forum published in the latest issue of the Journal of Alzheimer’s Disease reports new scientific findings and insights into the pathophysiological mechanisms that induce brain overexcitability and its deleterious clinical effects in AD patients. Such brain overexcitability can manifest as subclinical epileptiform activities often associated with a faster AD progression.

The Mini Forum has been promoted by The Electrophysiology Professional Interest Area (EPIA) Steering Committee of the International Society to Advance Alzheimer’s Research and Treatment (ISTAART).

The mission of EPIA is to disseminate recent findings and concepts about the use of neurophysiological techniques (e.g., TMS and EEG) for investigating the pathophysiology inducing brain excitability at different stages of AD and the discovery of quantitative measures (biomarkers) to be used in the assessment and treatment of AD patients.

The articles included in this Mini-Forum are the most recent editorial outcome of the EPIA initiative.

“These articles provide inspiring examples of preclinical and clinical research in AD using non-invasive brain stimulation and EEG techniques,” commented Guest Editor Dr. Claudio Babiloni, PhD, professor of Physiology at the Department of Physiology and Pharmacology “Vittorio Erspamer,” Sapienza University of Rome (Italy).

“The contents of those articles indicate the need to fill a gap in the actual neurobiological and clinical AD model. There is an urgent necessity for neurophysiological biomarkers to assess AD’s ‘dark side,’ whereby AD induces overexcitability in the brain neural networks with alterations in the regulation of vigilance and sleep-wake cycle.

These alterations affect patients’ consciousness levels, making them unable to follow a TV talk show or a quiet social conversation among relatives, for example, negatively impacting their daily quality of life and that of their caregivers.

This unique and original collection of preclinical studies in rodent models and clinical studies in AD patients covers the use of advanced neurophysiological techniques to model the pathophysiological mechanisms possibly explaining the symptoms hidden in the AD dark side.”

The National Institute of Aging and the Alzheimer’s Association have recently proposed a framework for the neurobiological diagnosis of AD for research applications.

This ATN© framework states that the AD diagnosis can be based on biomarkers derived from in vivo measurement of amyloidosis (“A”), tauopathy (“T”), and neurodegeneration (“N”) from the brain of patients living with AD. Research on cognitive deficits induced by those processes typically focuses on abnormalities in episodic memory and visuospatial skills (e.g., forgetfulness and spatial disorientation), mild cognitive impairment (MCI), and mild, moderate, or severe degrees of dementia.

The findings in this Mini-Forum provide the foundation for an extended model that could speed up research lines and discovery through further validation of pathophysiological “P” biomarkers. These are based on EEG activity/local field potentials reflecting 1) brain hyperexcitability for preclinical and clinical drug discovery pathways in AD and 2) the abnormal AD patients’ consciousness level (e.g., quiet vigilance stability) for clinical applications.

With the content of this Mini Forum in mind, Dr. Babiloni has proposed an AD model named “ATPNO,” including the symptoms and biomarkers of the AD dark side model.

“Remarkably, the ATN framework may be enriched with those pathophysiological ‘P’ biomarkers and the evaluation of vigilance, sleep-wake cycle, cognitive status, and abilities in the activities of daily living as a global clinical output (‘O’) specifically,” explained Dr. Babiloni.

This Mini Forum includes six articles covering relevant areas of the pathophysiological “P” biomarkers of brain hyperexcitability in AD. They provide significant examples of the preclinical (animal studies) and clinical research in AD using non-invasive brain stimulation and EEG techniques.

Examples of the enormous potential of these new research lines in preclinical and clinical models of AD include:

In the original article “TREM2 Deficiency Disrupts Network Oscillations Leading to Epileptic Activity and Aggravates Amyloid-β-Related Hippocampal Pathophysiology in Mice,” Milan Stoiljkovic, MD, PhD, Department of Comparative Medicine, Yale University School of Medicine, New Haven, CT, USA, and colleagues tested the contribution of the so-called triggering receptor expressed on myeloid cells-2 (TREM2) of the immune cells that defend our brain, the microglia, on the control of hippocampal network hyperexcitability in transgenic mice overproducing cerebral amyloidosis typical of AD.

The investigators used an elegant combination of brain electric stimulation and the recording of local field potentials in the hippocampus in mice with transgenic mutations reducing the functioning of the microglia. Those mice showed epileptiform activity in the brain, especially when transgenic mutations also induced abnormal amyloidosis in the brain.

Researchers Explore the “Dark Side” of Alzheimer’s Disease Revealing New Biomarkers

Such brain overexcitability can manifest as subclinical epileptiform activities often associated with a faster AD progression. Image is in the public domain

These findings suggest that the TREM2 plays a role not only in the regulation of hippocampal neuronal excitability during physiological conditions, but also in moderating that network hyperexcitability in the case of brain amyloid-beta overproduction. 

Recent evidence suggests that patients with mild to moderate AD without a known diagnosis of epilepsy might display preclinical (“silent”) epileptiform spikes during EEG recordings. These abnormal epileptiform activities occur predominantly during sleep and may be associated with accelerated disease progression.

In “Alzheimer’s Disease with Epileptiform EEG Activity: Abnormal Cortical Sources of Resting State Delta Rhythms in Patients with Amnesic Mild Cognitive Impairment,” Dr. Babiloni and colleagues explored the relationship between brain network hyperexcitability and AD-related neuropathology in patients with amnesic MCI due to AD (ADMCI). None of the patients had a clinical diagnosis of epilepsy.

About 15% of those patients showed silent, subclinical epileptiform EEG activity and greater AD-related amyloid neuropathology, thus suggesting more abnormal pathophysiological mechanisms underpinning the regulation of cortical arousal and quiet vigilance.

Other topics covered include:

  • Functional neurophysiological biomarkers of early-stage AD
  • Review of cortical overexcitability in AD and its association with clinical symptoms
  • Risk stratification of cognitive decline in people with late-onset epilepsy of unknown origin
  • Discussion of abnormal cortical sources of resting state delta rhythms in patients with amnesic MCI

“The articles in this Mini-Forum show the clinical relevance of the abnormalities in brain excitability and the related dysregulation of vigilance and sleep-wake cycle in those patients, and the need for effective biomarkers of those processes and adequate medications to treat them,” noted Dr. Babiloni.

“We are moving towards a new paradigm to better understand, measure, and treat the symptoms of the AD dark side.”

About this Alzheimer’s disease research news

Author: Diana MurraySource:IOS PressContact: Diana Murray – IOS Press
Image: The image is in the public domain

Original Research: The mini-forum edition of Journal of Alzheimer’s Disease is available online

TECH NEWS RELATED

New cleaning technique boosts electronic and photonic prospects of aluminum nitride

Cross-sectional microscopy images of molecular beam epitaxy-grown aluminum nitride on aluminum nitride templates. The black squares in (A) and (E) mark the regions where the corresponding magnified images (B to D and F to H) are taken. The white notches in (A) and (E) indicate the growth interfaces. The ...

View more: New cleaning technique boosts electronic and photonic prospects of aluminum nitride

Utilizing chemo-mechanical oscillations to mimic protocell behavior in manufactured microcapsules

Credit: Oleg E. Shklyaev et al, Matter (2022). DOI: 10.1016/j.matt.2022.06.063 The complexity of life on Earth was derived from simplicity: From the first protocells to the growth of any organism, individual cells aggregate into basic clumps and then form more complex structures. The earliest cells lacked complicated biochemical machinery; ...

View more: Utilizing chemo-mechanical oscillations to mimic protocell behavior in manufactured microcapsules

Research team develops a cleaner, more cost-effective way to make useful industrial chemicals

Credit: Tony Jin et al, Angewandte Chemie International Edition (2022). DOI: 10.1002/anie.202207206 Two renewable resources—cellulose from wood pulp and chitin from the shells of crabs, lobsters and other crustaceans—are known to industrial chemists for their potential for creating highly versatile nanocrystals, useful for making pharmaceuticals, cosmetics, industrial additives and ...

View more: Research team develops a cleaner, more cost-effective way to make useful industrial chemicals

Climate change made summer drought 20 times more likely

Credit: Pixabay/CC0 Public Domain Drought that stretched across three continents this summer—drying out large parts of Europe, the United States and China—was made 20 times more likely by climate change, according to a new study. Drought dried up major rivers, destroyed crops, sparked wildfire, threatened aquatic species and led ...

View more: Climate change made summer drought 20 times more likely

Study: Removing GRE requirement does not undermine student success

Credit: Unsplash/CC0 Public Domain In 2019, Boston University School of Public Health (BUSPH) eliminated the Graduate Record Examination as a requirement for admission to the school’s graduate programs for a pilot period of three years. The school’s decision was fueled by a growing body of data that indicated that ...

View more: Study: Removing GRE requirement does not undermine student success

Earth System Grid Federation launches effort to upgrade climate projection data system

A simulation of the planet from the DOE Energy Exascale Earth System Model, one of the large-scale models incorporated in the Earth System Grid Federation led by DOE’s Oak Ridge, Argonne and Lawrence Livermore national laboratories. Credit: LLNL, U.S. Dept. of Energy The Earth System Grid Federation, a multi-agency ...

View more: Earth System Grid Federation launches effort to upgrade climate projection data system

Some everyday materials have memories, and now they can be erased

In this study, the research team tracked the locations of 25,000 tiny particles that make up a two-dimensional disordered solid. Groups of particles rearrange as the solid is deformed. This diagram depicts when particles are rearranged as the material is deformed in one direction (left) or the opposite direction ...

View more: Some everyday materials have memories, and now they can be erased

Shocking Study Finds Decreased Proteins – Not Amyloid Plaques – Cause Alzheimer’s Disease

The prevailing theory is that Alzheimer’s disease is caused by the buildup of amyloid plaques in the brain. However, new research finds that it is actually caused by a decline in levels of a specific protein. New research on patients with mutations published in the Journal of Alzheimer’s Disease. ...

View more: Shocking Study Finds Decreased Proteins – Not Amyloid Plaques – Cause Alzheimer’s Disease

Logging down the value chain raises future forest sustainability concerns

SpaceX capsule heads to space station ferrying NASA crew and Russian

Documentary featuring Professor Sara Seager wins Emmy Award

Petting Dogs Engages the Social Brain, According to Neuroimaging

Do You Act Before You Think or Think Before You Act?

A Possible Brain Mechanisms Behind COVID-19 Delirium

Researchers develop new tool for targeted cell control

Researchers pioneer nanoprinting electrodes for customized treatments of neurological disorders

Study shows challenge of promoting citizen science to help prevent disasters caused by flooding

Crew Dragon launches safely, carrying first Russian from US soil in 20 years

Click! 2022 Nobel goes to chemistry made simple and reliable

A Nose to Diagnose: Improving Parkinson’s Diagnosis

OTHER TECH NEWS

Top Car News Car News