Benedict C. Albensi

Nova Southeastern University | NSU · Department of Pharmaceutical Sciences

BACKGROUND: Mitochondrial transplantation is an emerging technique focused until now on ischemia-reperfusion injuries and rare mitochondrial mutation diseases. Platelets are the most common immune cells in the blood and emit mitochondria inside extracellular vesicles (mitlets) during activation or at their end-of-life. Mitlets are preferentially ab...

Introduction: In a previous retrospective study using postmortem human brain tissues, we demonstrated that loss of Cholinergic Receptor Muscarinic 1 (CHRM1) in the temporal cortex of a subset of Alzheimer’s patients was associated with poor survival, whereas similar loss in the hippocampus showed no such association. Mitochondrial dysfunction under...

Introduction: Cholinergic Receptor Muscarinic 1 (CHRM1) is a G protein-coupled acetylcholine (ACh) receptor predominantly expressed in the cerebral cortex. In a retrospective postmortem brain tissues-based study, we demonstrated that severely (≥50% decrease) reduced CHRM1 proteins in the temporal cortex of Alzheimer’s patients significantly correla...

Alzheimer’s disease (AD) is a progressive, neurodegenerative disorder that affects memory, thinking, behavior, and other cognitive functions. Although there is no cure, detecting AD early is important for the development of a therapeutic plan and a care plan that may preserve cognitive function and prevent irreversible damage. Neuroimaging, such as...

Alzheimer's disease (AD) is characterized by the accumulations of amyloid beta and neurofibrillary tangles in brain tissue; however, AD is multifactorial and different etiopathogenic mechanisms involves that can affect mitochondrial function that are associated with AD. In the current study, we investigated the effect of lithium on mitochondrial fu...

Post-menopausal women are at a higher risk of developing Alzheimer’s disease (AD) than males. The higher rates of AD in women are associated with the sharp decline in the estrogen levels after menopause. Estrogen has been shown to downregulate inflammatory cytokines in the central nervous system (CNS), which has a neuroprotective role against neuro...

Disturbances in the brain's capacity to meet its energy demand increase the risk of synaptic loss, neurodegeneration, and cognitive decline. Nutritional and metabolic interventions that target metabolic pathways combined with diagnostics to identify deficits in cerebral bioenergetics may therefore offer novel therapeutic potential for Alzheimer's d...

Background: Dysfunction of cholinergic neurotransmission is a hallmark of Alzheimer's disease (AD); forming the basis for using acetylcholine (ACh) esterase (AChE) inhibitors to mitigate symptoms of ACh deficiency in AD. The Cholinergic Receptor Muscarinic 1 (CHRM1) is highly expressed in brain regions impaired by AD. Previous analyses of postmort...

Background: We previously introduced a machine learning-based Alzheimer's Disease Designation (MAD) framework for identifying AD-related metabolic patterns among neurodegenerative subjects. Objective: We sought to assess the efficiency of our MAD framework for tracing the longitudinal brain metabolic changes in the prodromal stage of AD. Method...

The mitochondrial theory of aging is characterized by mitochondrial electron transport chain dysfunction. As a hallmark of aging, an increasing number of investigations have attempted to improve mitochondrial function in both aging and age-related disease. Emerging from these attempts, methods involving mitochondrial isolation, transfusion, and tra...

Observational studies suggest that nutritional factors have a potential cognitive benefit. However, systematic reviews of randomised trials of dietary and nutritional supplements have reported largely null effects on cognitive outcomes and have highlighted study inconsistencies and other limitations. In this Personal View, the Nutrition for Dementi...

Alzheimer's disease (AD) is one of the biggest human health threats due to increases in aging of the global population. Unfortunately, drugs for treating AD have been largely ineffective. Interestingly, downregulation of macroautophagy (autophagy) plays an essential role in AD pathogenesis. Therefore, targeting autophagy has drawn considerable atte...

Background: Alzheimer's disease (AD) is progressive, neurodegenerative disorder, characterized by memory loss and cognitive decline. Advanced age and female sex are the most prominent risk factors. Although epidemiological and clinical studies have provided evidence for sex differences, relevant molecular mechanisms are not well characterized. To...

The coronavirus disease that presumably began in 2019 (COVID-19) is a highly infectious disease caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and has resulted in a pandemic. Initially, COVID-19 was thought to only affect respiration. However, accumulating evidence shows a wide range of neurological symptoms are also ass...

Nuclear factor erythroid 2-related factor 2 (Nrf2) is an important transcription factor that reduces oxidative stress. When reactive oxygen species (ROS) or reactive nitrogen species (RNS) are detected, Nrf2 translocates from the cytoplasm into the nucleus and binds to the antioxidant response element (ARE), which regulates the expression of antiox...

The transcription factor nuclear factor kappa B (NF-κB) is highly expressed in almost all types of cells. NF-κB is involved in many complex biological processes, in particular in immunity. The activation of the NF-κB signaling pathways is also associated with cancer, diabetes, neurological disorders and even memory. Hence, NF-κB is a central factor...

Alzheimer’s disease (AD) is a debilitating neurological disorder, and currently, there is no cure for it. Several pathologic alterations have been described in the brain of AD patients, but the ultimate causative mechanisms of AD are still elusive. The classic hallmarks of AD, including amyloid plaques (Aβ) and tau tangles (tau), are the most studi...

Current treatments targeting amyloid beta in Alzheimer's disease (AD) have minimal efficacy, which results in a huge unmet medical need worldwide. Accumulating data suggest that brain mitochondrial dysfunction play a critical role in AD pathogenesis. Targeting cellular mechanisms associated with mitochondrial dysfunction in AD create a novel approa...

Persons with dementia (PWD) make up a large portion of the long-term care (LTC) population the world over. Before a global pandemic swept the world, governments and healthcare providers struggled with how to best care for this unique population. One of the greatest challenges is a PWD’s tendency to “walk with purpose” and exhibit unsafe wayfinding...

Alzheimer’s disease (AD) is a debilitating neurological disorder, and currently, there is no cure for it. Several pathologic alterations have been described in the brain of AD patients, but the ultimate causative mechanisms of AD are still elusive. The classic hallmarks of AD, including am-yloid plaques (Aβ) and tau tangles (tau), are the most stud...

Objectives: Although choline is essential for brain development and neural function, the effect of choline on retina function is not well understood. This study examined the effects of choline on neural tissues of brain and retina, and membrane phospholipid (PL) composition during fetal development. Methods: Pregnant C57BL/6 mice were fed one of...

Hyperammonemia is very toxic to the brain, leading to inflammation, disruption of brain cellular energy metabolism and cognitive function. However, the underlying mechanism(s) for these impairments is still not fully understood. This study investigated the effects of ammonia in hippocampal astroglia derived from C57BL/6 mice. Parameters measured in...

The creatine (Cr) energy system has been implicated in Alzheimer’s disease (AD), including reductions in brain phosphoCr and Cr kinase, yet no studies have examined the neurobehavioral effects of Cr supplementation in AD, including the 3xTg mouse model. This studied investigated the effects of Cr supplementation on spatial cognition, plasticity- an...

Randomized clinical trials (RCT) involve labor-intensive, highly regulated, and controlled processes intended to transform scientific concepts into clinical outcomes. To be effective and targeted, it is imperative they include those populations who would most benefit from those outcomes. Alzheimer's disease (AD) is most detrimental to the aging pop...

Alzheimer’s disease (AD) is a major public health concern worldwide. Advanced age and female sex are two of the most prominent risk factors for AD. AD is characterized by progressive neuronal loss, especially in the cortex and hippocampus, and mitochondrial dysfunction has been proposed to be an early event in the onset and progression of the disea...

Dementia is an umbrella term—caused by a large number of specific diagnoses, including several neurodegenerative disorders. Alzheimer's disease (AD) is now the most common cause of dementia in advanced countries, while dementia due to neurosyphilis was the leading cause a century ago. Many challenges remain for diagnosing dementia definitively. Som...

Biomarkers of aging are urgently needed to identify individuals at high risk of developing age-associated disease or disability. Growing evidence from population-based studies points to whole-body magnetic resonance ima-ging's (MRI) enormous potential for quantifying subclinical disease burden and for assessing changes that occur with aging in all...

A large body of literature supports the idea that nuclear factor kappa B (NF-κB) signaling contributes to not only immunity, but also inflammation, cancer, and nervous system function. However, studies on NF-κB activity in mitochondrial function are much more limited and scattered throughout the literature. For example, in 2001 it was first publish...

Alzheimer's disease (AD) is a progressive age-related neurodegenerative disease. Although neurofibrillary tangles and amyloid beta are classic hallmarks of AD, the earliest deficits in AD progression may be caused by unknown factors. One suspected factor has to do with brain energy metabolism. To investigate this factor, brain metabolic activity in...

Recent reports in pathophysiology of neurodegenerative diseases (ND) have linked nuclear lamina degradation/deficits to neuronal cell death. Lamin-B1 damage is specifically involved in this process leading to nuclear envelope invagination and heterochromatin rearrangement. The underlying mechanisms involved in these events are not yet defined. In...

Alzheimer's disease (AD), the most common form of dementia, is thought to be associated with multiple factors, where the greatest risk factor is aging. Several traditional views attribute the cause of AD to genetic heritability, reduced synthesis of the neurotransmitter acetylcholine, the accumulation of a toxic protein known as amyloid β (Aβ) pept...

In Alzheimer's disease (AD), characterized by cognitive deterioration, synaptic alterations are frequently reported. The TgCRND8 model, in which mice develop AD-like amyloid β plaque formation, has been used to investigate the effects of amyloidosis on synaptic function. Background strain impacts the behavioral and neuropathological phenotype of mi...

Alzheimer's disease and related dementias (ADRDs) are a global crisis facing the aging population and society as a whole. With the numbers of people with ADRDs predicted to rise dramatically across the world, the scientific community can no longer neglect the need for research focusing on ADRDs among underrepresented ethnoracial diverse groups. The...

In Alzheimer's disease (AD), characterized by cognitive deterioration, synaptic alterations are frequently reported. The TgCRND8 model, in which mice develop AD-like amyloid β plaque formation, has been used to investigate the effects of amyloidosis on synaptic function. Background strain impacts the behavioral and neuropathological phenotype of mi...

Recent reports in pathophysiology of neurodegenerative diseases (ND) have linked nuclear lamina degradation/deficits to neuronal cell death. Lamin-B1 cleavage is specifically involved in this process that leads to nuclear envelope invagination and heterochromatin rearrangement. Although the contribution of oxidative stress in induction of these cha...

Until very recently, the conventional optical resolution limits for far-field infrared (IR) imaging were ~5-10 µm, given the 2-25 µm wavelengths and the typical optics of mid-IR microscopes. In 2011, the diffraction limit for far-field IR was achieved with synchrotron source light, high numerical aperture (NA) optics, and a focal plane array detect...

Background Alzheimer's disease (AD) is a neurodegenerative disorder that affects over 45 million people worldwide. Patients with severe AD require help with daily activities and show severe memory impairment. Currently, donepezil is one of two drugs approved by FDA and Health Canada for the treatment of severe AD (MMSE score <10). It is prescribed...

Dementia is a growing public health concern in Canada. This epidemic is linked to huge human and economic costs. The number of Manitobans (65+) with dementia in 2045 (47,021), representing 2.58% of the Manitoban population, will be 2.3 times that of the year 2015 (20,235). The number of cases of dementia in Manitoba grew by 20.7% from 2015 to 2025,...

Aims: Abnormalities in mitochondrial function under diabetic conditions can lead to deficits in function of cortical neurons and their support cells exhibiting a pivotal role in the pathogenesis of several neurodegenerative disorders, including Alzheimer's disease. We aimed to assess mitochondrial respiration rates and membrane potential or H2O2 g...

The brain has a high demand for energy, of which creatine (Cr) is an important regulator. Studies document neurocognitive benefits of oral Cr in mammals, yet little is known regarding their physiological basis. This study investigated the effects of Cr supplementation (3%, w/w) on hippocampal function in male C57BL/6 mice, including spatial learnin...

Alzheimer's disease (AD) is the most common late onset neurodegenerative disorder with indications that women are disproportionally affected. Mitochondrial dysfunction has been one of the most discussed hypotheses associated with the early onset and progression of AD, and it has been attributed to intraneuronal accumulation of amyloid β (Aβ). It wa...

A diagnosis of Alzheimer's disease (AD), a neurodegenerative disorder accompanied by severe functional and cognitive decline, is based on clinical findings, with final confirmation of the disease at autopsy by the presence of amyloid-β (Aβ) plaques and neurofibrillary tangles. Given that microstructural brain alterations occur years prior to clinic...

Visinin-like proteins (VILIPs) belong to the calcium sensor protein family. VILIP-1 has been examined as a cerebrospinal fluid biomarker and as a potential indicator for cognitive decline in Alzheimer’s disease (AD). However, little is known about VILIP-3 protein biochemistry. We performed co-immunoprecipitation experiments to examine whether VILIP...

Mitochondria are the primary source for energy generation in the cell, which manifests itself in the form of the adenosine triphosphate (ATP). Nicotinamide dinucleotide (NADH) molecules are the first to enter the so-called electron transport chain or ETC of the mitochondria. The ETC represents a chain of reducing agents organized into four major pr...

Although, better known for its role in inflammation, the transcription factor nuclear factor kappa B (NF-κB) has more recently been implicated in synaptic plasticity, learning, and memory. This has been, in part, to the discovery of its localization not just in glia, cells that are integral to mediating the inflammatory process in the brain, but al...

Ammonia is known to be a potent neurotoxin that causes severe negative effects on the central nervous system. Excessive ammonia levels have been detected in the brain of patients with neurological disorders such as Alzheimer disease (AD). Therefore, ammonia could be a factor contributing to the progression of AD. In this review, we provide an intro...

Calcium homeostasis is an essential physiological process requiring tight control in the normal cell. The dysregulation of calcium homeostasis may play a key role in the onset of Alzheimer's disease (AD) and other disorders, whether through the loss of calcium binding or calcium sensing capacity. Calbindin D28k (CB-D28k), a calcium binding protein...

Traumatic brain injury (TBI) has become a significant medical and social concern within the last 30 years. TBI has acute devastating effects, and in many cases, seems to initiate long-term neurodegeneration. With advances in medical technology, many people are now surviving severe brain injuries and their long term consequences. Post trauma effects...

Mitochondrial membrane potential (mtMP) is critical for maintaining the physiological function of respiratory chain to generate ATP. This study characterized inter-relationship between mtMP, using safranin and TMRM, and mitochondrial respiratory activity and established a protocol for functional analysis of mitochondrial bioenergetics in a multi-se...

Research has identified several transcription factors that regulate activity-dependent plasticity and memory, with cAMP-response element binding protein (CREB) being the most well-studied. In neurons, CREB activation is influenced by the transcription factor nuclear factor kappa B (NF-κB), considered central to immunity but more recently implicated...

Besides mental dysfunctions, Alzheimer's disease (AD) may impair muscle function. Creatine supplementation (CR) can enhance skeletal muscle mass and function in sarcopenia and muscular dystrophies, but has yet to be studied in AD. We examined the effect of oral CR on muscle amino acids (AA) level in an AD model. 24 triple transgenic (3×Tg, ~8 mo ol...

Transcription factors are known to play multiple roles in cellular function. Investigators report that factors such as early growth response (Egr) protein and nuclear factor kappa B (NF-κB) are activated in the brain during cancer, brain injury, inflammation, and/or memory. To explore NF-κB activity further, we investigated the transcriptomes of hi...

Oscillatory activity is inherent in many types of normal cellular function. Importantly, oscillations contribute to cellular network activity and cellular decision making, which are driving forces for cognition. Theta oscillations have been correlated with learning and memory encoding and gamma oscillations have been associated with attention and w...

Although traditionally associated with immune function, the transcription factor nuclear factor kappa B (NF-κB) has garnered much attention in recent years as an important regulator of memory. Specifically, research has found that NF-κB, localized in both neurons and glia, is activated during the induction of long-term potentiation (LTP), a paradig...

While the basis of neuronal degeneration in Alzheimer's disease (AD) continues to be debated, the amyloid cascade hypothesis remains central. Amyloid plaques are a required pathological marker for post mortem diagnosis, and Aβ peptide is regarded by most as a critical trigger at the very least. We present spectrochemical image analysis of brain tis...

Adenosine is a neuromodulator with its level increasing up to 100-fold during ischemic events, and attenuates the excitotoxic neuronal injury. Adenosine is produced both intracellularly and extracellularly, and nucleoside transport proteins transfer adenosine across plasma membranes. Adenosine levels and receptor-mediated effects of adenosine are r...

Background Adenosine has neuromodulatory effects in animal stroke models. We previously showed that human equilibrative nucleoside transporter 1 (hENT1) over expression decreases extracellular adenosine action. Caffeine is adenosine receptor antagonist. Objective To compare the effect of ENT1 over expression on cerebral blood flow (CBF) and subsequ...

Adenosine, through activation of its A(1) receptors, has neuroprotective effects during hypoxia and ischemia. Recently, using transgenic mice with neuronal expression of human equilibrative nucleoside transporter 1 (hENT1), we reported that nucleoside transporter-mediated release of adenosine from neurons was not a key mechanism facilitating the ac...

Calbindin D28k is a calcium buffer and sensor. It is composed of six EF-hands (calcium binding domains) but only four of them can bind calcium. Calbindin D28k can also bind zinc ions. We used computational modelling to understand why EF-hands 2 and 6 lose their calcium binding ability. We also docked zinc ions to the protein to investigate the pote...

Background: Nuclear factor kappa B (NF-κB) is a transcription factor typically expressed with two specific subunits (p50, p65). Investigators have reported that NF-κB is activated during the induction of in vitro long term potentiation (LTP), a paradigm of synaptic plasticity and correlate of memory, suggesting that NF-κB may be necessary for some...

The dietary intake of polyunsaturated fatty acids (PUFAs), e.g., docosahexaenoic acid, eicosapentaenoic acid and arachidonic acid, is reflected in the biochemical makeup of tissues. In the course of analyzing mouse retina and brain tissue with Fourier Transform infrared (FTIR) microspectroscopy, we discovered that special considerations are require...

Activation of adenosine A1 receptors has neuroprotective effects in animal stroke models. Adenosine levels are regulated by nucleoside transporters. In vitro studies showed that neuron-specific expression of human equilibrative nucleoside transporter 1 (hENT1) decreases extracellular adenosine levels and adenosine A1 receptor activity. In this stud...

Changing the strength of synaptic connections between neurons is a process by which memory traces are encoded and stored in the nervous system. Evidence to date suggests that long term memory encoding and storage are dependent on mRNA translation and protein synthesis. Studies over the years have identified key signaling molecules involved in proce...

Transcription factors are specialized proteins that bind to specific DNA sequences, thereby controlling the movement (a.k.a. transcription) of genetic information from DNA to mRNA. In so doing, transcription factors can promote or repress the recruitment of RNA polymerase to specific genes thereby regulating gene expression.

The critical questions into the cause of neural degeneration, in Alzheimer disease and other neurodegenerative disorders, are closely related to the question of why certain neurons survive. Answers require detailed understanding of biochemical changes in single cells. Fourier transform infrared microspectroscopy is an excellent tool for biomolecula...

Adenosine concentrations are regulated by purinergic enzymes and nucleoside transporters. Transgenic mice with neuronal expression of human equilibrative nucleoside transporter 1 (hENT1) have been generated (Parkinson et al., 2009 [7]). The present study tested the hypothesis that mice homozygous and heterozygous for the transgene exhibit differenc...

J. Neurochem. (2011) 10.1111/j.1471-4159.2011.07242.x Activation of adenosine A1 receptors inhibits excitatory synaptic transmission. Equilibrative nucleoside transporters (ENTs) regulate extracellular adenosine levels; however, the role of neuronal ENTs in adenosine influx and efflux during cerebral ischemia has not been determined. We used mice w...

Pathological hallmarks of Alzheimer's disease include memory deficits, accumulation of amyloid beta (Abeta) plaques, the appearance of neurofibrillary tangles, and dysregulation of calcium homeostasis, which has been linked to mutations in the presenilin gene that code for presenilin (PS) proteins. PSs are a family of multi-pass transmembrane prote...

Alzheimer’s disease (AD) is a progressive neurodegenerative disorder that has been characterized by gross cortical atrophy, cellular neurodegeneration, reactive gliosis, and the presence of microscopic extracellular amyloid plaques and intracellular neurofibrillary tangles. Earlier diagnoses of AD would be in the best interest of managing the patie...