Dimitrios Kapogiannis

Dimitrios Kapogiannis
  • M.D.
  • Clinical Investigator at National Institutes of Health

About

235
Publications
49,269
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12,920
Citations
Current institution
National Institutes of Health
Current position
  • Clinical Investigator
Additional affiliations
January 2009 - present
July 2006 - December 2008
National Institute of Neurological Disorders and Stroke
Position
  • Clinical Fellow

Publications

Publications (235)
Article
Over the past few decades, extensive basic, translational and clinical research has been devoted to deciphering the physiological and pathogenic roles of extracellular vesicles (EVs) in the nervous system. The presence of brain cell-derived EVs in the blood, carrying diverse cargoes, has enabled the development of predictive, diagnostic, prognostic...
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Background Insulin Resistance (IR) is implicated in brain aging and Alzheimer’s disease (AD) pathogenesis. Dietary changes may promote brain health in older adults with metabolic abnormalities. An extensive animal literature suggests pro‐cognitive and beneficial systemic and brain effects of intermittent fasting (IF) that may mitigate AD risk. We c...
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Autobiographical memory is diminished in patients with behavioural variant of frontotemporal dementia (bvFTD), and research has focused on the hampered ability of patients to retrieve specific memories. In this study, we implemented a methodology seeking to provide a qualitative analysis of autobiographical specificity. We invited patients with bvF...
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Small membranous extracellular vesicles (EV) incorporate proteins and nucleic acids from the parent cell. Proteins exposed on EV surface are dictated by cellular origin and biogenesis pathway. To better understand the EV origin and function, it is important to develop methods that reveal surface protein composition of heterogeneous EV populations i...
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Background Apolipoprotein E ( APOE ) ε4 allele is the strongest genetic risk factor for late onset Alzheimer’s disease (AD). This case-cohort study used targeted plasma biomarkers and large-scale proteomics to examine the biological mechanisms that allow some APOE ε4 carriers to maintain normal cognitive functioning in older adulthood. Methods APO...
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Despite most monoclonal antibodies against Aβ in Alzheimer’s failed to demonstrate efficacy, the newest antibodies showed statistically significant clinical effects. We conducted a systematic review and meta-analysis to assess the efficacy, target engagement, and safety of anti-Aβ antibodies in sporadic AD including phase III RCTs published up to N...
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Mitochondria are essential for supporting the high metabolic demands that are required for brain function. Impairments in mitochondria have been linked to age-related decline in brain functions. Here, we investigate whether the mitochondrial respiratory capacity of brain cells is changed in cognitive aging. We used a rat model of normal cognitive a...
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Adults with prediabetes are at risk for Alzheimer's Disease and Related Dementia (ADRD). While exercise may lower ADRD risk, the exact mechanism is unclear. We tested the hypothesis that short‐term exercise would raise neuronal insulin signaling and pro‐BDNF in neuronal extracellular vesicles (nEVs) in prediabetes. Twenty‐one older adults (18F, 60....
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INTRODUCTION Cancer is inversely associated with cognitive impairment. Whether this is due to statistical handling of attrition (death and censoring) is unknown. METHODS We quantified associations between cancer history and incident cognitive impairment among Health, Aging, and Body Composition Study participants without baseline cognitive impairm...
Article
Introduction & Objective: Prediabetes raises Alzheimer’s Disease and Related Dementia (ADRD) risk. While exercise may lower ADRD risk, it is unclear if it does so by raising brain insulin sensitivity and/or brain derived neurotrophic growth factor (BDNF). We hypothesized that short-term exercise would raise brain insulin signaling and BDNF from neu...
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Previous research suggest that extracellular vesicles (EVs) secreted by brain neurons carry L1CAM and circulate in peripheral blood, coexisting with L1CAM‐positive EVs from peripheral cellular sources and free L1CAM peptides (top left). These other versions of L1CAM in blood challenge the approach of targeting L1CAM for the immunoaffinity isolation...
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In this study, we offer a comprehensive assessment of the phenomenological experience of patients with behavioral-variant frontotemporal dementia (bvFTD) upon retrieval of autobiographical memory. We invited patients with bvFTD and control participants to retrieve autobiographical memories and rate, for each memory, its phenomenological characteris...
Article
Objectives: To assess whether the rate of change in synaptic proteins isolated from neuronally enriched extracellular vesicles (NEVs) is associated with brain and retinal atrophy in people with multiple sclerosis (MS). Methods: People with MS were followed with serial blood draws, MRI (MRI), and optical coherence tomography (OCT) scans. NEVs wer...
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Objective Mitochondrial impairments have been implicated in the pathogenesis of Fragile X‐associated tremor/ataxia syndrome (FXTAS) based on analysis of mitochondria in peripheral tissues and cultured cells. We sought to assess whether mitochondrial abnormalities present in postmortem brain tissues of patients with FXTAS are also present in plasma...
Article
Brain iron deficiency (ID) and, to a degree, systemic ID have been implicated in restless leg syndrome (RLS) pathogenesis. Previously, we found increased ferritin in neuron‐derived extracellular vesicles (NDEVs) in RLS, suggesting a mechanism for depleting intracellular iron by secreting ferritin‐loaded NDEVs. In this study, we hypothesized that in...
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Analysis of blood-based indicators of brain health could provide an understanding of early disease mechanisms and pinpoint possible intervention strategies. By examining lipid profiles in extracellular vesicles (EVs), secreted particles from all cells, including astrocytes and neurons, and circulating in clinical samples, important insights regardi...
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Long COVID (LongC) is associated with a myriad of symptoms including cognitive impairment. We reported at the beginning of the COVID-19 pandemic that neuronal-enriched or L1CAM+ extracellular vesicles (nEVs) from people with LongC contained proteins associated with Alzheimer’s disease (AD). Since that time, a subset of people with prior COVID infec...
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Background The potential of ChatGPT in medical diagnosis has been explored in various medical conditions. Objective We assessed whether ChatGPT can contribute to the diagnosis of Alzheimer’s disease (AD). Methods We provided ChatGPT with four generated cases (mild, moderate, or advanced stage AD dementia, or mild cognitive impairment), including...
Preprint
Neuronal insulin resistance is linked to the pathogenesis of Parkinson’s disease through unclear, but potentially targetable, mechanisms. We delineated neuronal and glial mechanisms of insulin resistance and glucagon-like 1 peptide (GLP-1) receptor agonism in human iPSC models of synucleinopathy, and corroborated our findings in patient samples fro...
Article
Background Mounting evidence correlates the propagation of hyperphosphorylated tau (pTau) along synaptically connected networks in the brain with progressive cognitive decline in Alzheimer’s Disease (AD). Recent findings have highlighted extracellular vesicle (EV)s in enabling transcellular transmission of pathological tau and identified the partia...
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Background In the era of Precision Medicine, extracellular vesicles (EVs) exhibit great potential for the theragnostic of brain disorders such as Alzheimer’s disease (AD), a complex disease with no effective treatment and poorly understood risk factors, where pathological heterogeneity and diverse clinical presentations complicate the development o...
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Financial decision‐making requires trading off between guaranteed and probabilistic outcomes and between immediate and delayed ones. While research has demonstrated that patients with behavioural‐variant frontotemporal dementia (bvFTD) prefer immediate rewards at the expense of future ones (i.e. temporal discounting), little is known about how pati...
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Observational studies have consistently found dementia to be inversely related to cancer, where presence of cancer predicts lower dementia risk, and presence of dementia predicts lower cancer risk. This “inverse comorbidity” relationship is of interest as an avenue to potentially identify novel intervention targets to develop for both conditions. H...
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Fragile X (FMR1) premutation is a common mutation that affects about 1 in 200 females and 1 in 450 males and can lead to the development of fragile-X-associated tremor/ataxia syndrome (FXTAS). Although there is no targeted, proven treatment for FXTAS, research suggests that sulforaphane, an antioxidant present in cruciferous vegetables, can enhance...
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Background Cognitive decline in Alzheimer’s disease (AD) is associated with hyperphosphorylated tau (pTau) propagation between neurons along synaptically connected networks, in part via extracellular vesicles (EVs). EV biogenesis is triggered by ceramide enrichment at the plasma membrane from neutral sphingomyelinase2 (nSMase2)-mediated cleavage of...
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We asked 44 French and 42 Lebanese participants with Alzheimer’s disease (AD) who lived in their own homes to rate their depression and anxiety during the late fall/early winter 2020 lockdown and compared their responses. We also asked caregivers to quantify the frequency of visits that participants received from family members during the lockdown....
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Background: While affective disturbances are a key symptomatic indicator of behavioural variant frontotemporal dementia (bvFTD), little is known about how patients process the emotional load of their autobiographical (i.e. personal) memories. Methods: We assessed the interplay of emotional regulation and autobiographical memory by inviting 18 bv...
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Introduction: Alzheimer’s disease (AD) is currently defined according to biomarkers reflecting the core underlying neuropathological processes: Aβ deposition, Tau, and neurodegeneration (ATN). The soluble phase of plasma and plasma neuron-derived extracellular vesicles (NDEVs) are increasingly being investigated as sources of biomarkers. The aim of...
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Background Neuron-derived extracellular vesicles (NDEVs) in blood may be used to derive biomarkers for the effects of exercise in Alzheimer’s disease (AD). For this purpose, we studied changes in neuroprotective proteins proBDNF, BDNF, and humanin in plasma NDEVs from patients with mild to moderate AD participating in the randomized controlled tria...
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Extracellular vesicles and particles (EVPs) are secreted by organs across the body into different circulatory systems, including the bloodstream, and reflect pathophysiologic conditions of the organ. However, the heterogeneity of EVPs in the blood makes it challenging to determine their organ of origin. We hypothesized that small (s)EVPs (<100 nm i...
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Introduction: Impaired autophagy is a pathogenic mechanism in the synucleinopathies. Sirolimus, a potent mTOR inhibitor and autophagy activator, had no beneficial effects in a randomized placebo-controlled trial in patients with multiple system atrophy (MSA). Whether sirolimus effectively inhibited brain mTOR activity was unknown. We aimed to eval...
Preprint
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Background Cognitive decline in Alzheimer’s disease (AD) is associated with prion-like tau propagation between neurons along synaptically connected networks, in part via extracellular vesicles (EV). EV biogenesis is triggered by ceramide enrichment at the plasma membrane from neutral sphingomyelinase2(nSMase2)-mediated cleavage of sphingomyelin. We...
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While research has shown a distrusted sense of the self in patients with behavioral variant frontotemporal dementia (bvFTD), little is known about how patients describe their self-image. We used the "Who am I?" task to invite patients with bvFTD and control participants to produce statements beginning with "I am…." We distinguished between statemen...
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Aims: Blood biomarkers can improve drug development for Alzheimer’s disease (AD) and its treatment. Neuron-derived extracellular vesicles (NDEVs) in plasma offer a minimally invasive platform for developing novel biomarkers that may be used to monitor the diverse pathogenic processes involved in AD. However, NDEVs comprise only a minor fraction of...
Preprint
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Background Neuron-derived extracellular vesicles (NDEVs) in blood may be used to derive biomarkers for effects of exercise in Alzheimer’s disease (AD). For this purpose, we studied changes in neuroprotective proteins proBDNF, BDNF and humanin in plasma NDEVs from patients with mild to moderate AD participating in the randomized controlled trial (RC...
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Studying mitochondrial respiration capacity is essential for gaining insights into mitochondrial functions. In frozen tissue samples, however, our ability to study mitochondrial respiration is restricted by damage elicited to the inner mitochondrial membranes by freeze-thaw cycles. We developed an approach that combines multiple assays and is tailo...
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Background Extracellular vesicles (EVs), including small EVs (sEVs) such as exosomes, exhibit great potential for the diagnosis and treatment of brain disorders, representing a valuable tool for precision medicine. The latter demands high-quality human biospecimens, especially in complex disorders in which pathological and specimen heterogeneity, a...
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(1) Background and aims: Amyloidosis due to aggregation of amyloid-β (Aβ42) is a key pathogenic event in Alzheimer’s disease (AD), whereas aggregation of mature islet amyloid polypeptide (IAPP37) in human islets leads to β-cell dysfunction. The aim of this study is to uncover potential biomarkers that might additionally point to therapy for early A...
Article
Alzheimer’s Disease (AD) is the most common form of dementia worldwide and is characterized by progressive neurodegeneration and cognitive decline, putatively driven by the accumulation Amyloid‐b and hyperphosphorylated Tau. Clinical trial successes focusing on reducing Amyloid‐b plaque levels in patient brains have been modest, spurring a renewed...
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Declining nicotinamide adenine dinucleotide (NAD+) concentration in the brain during aging contributes to metabolic and cellular dysfunction and is implicated in the pathogenesis of aging‐associated neurological disorders. Experimental therapies aimed at boosting brain NAD+ levels normalize several neurodegenerative phenotypes in animal models, mot...
Article
Brain insulin signaling, as measured by insulin signaling proteins in neuronal enriched extracellular vesicles (nEVs), has previously been associated with gray matter (GM) volume in the temporal lobe of nondemented older adults and in multiple brain regions in those with Alzheimer’s clinical syndrome (Walker et al, 2021; Mullins et al, 2017). We so...
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Sodium-glucose cotransporter-2 inhibitors (SGLT2is), such as empagliflozin, lower blood glucose in type 2 diabetes mellitus and improve cardiorenal outcomes regardless of diabetes presence. Whether SGLT2is exert any effects on the brain’s metabolism has not been studied. We conducted a single-arm clinical trial to investigate the effects of once da...
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The decline of autobiographical memory in Alzheimer’s disease (AD) is mainly characterized by overgenerality. While there is a large body of research on autobiographical overgenerality in AD, this research has mainly assessed retrieval with a dichotomy between specific vs. general retrieval. To go beyond this dichotomy, we assessed several degrees...
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Our perception of distinct structures in brain cells and understanding of their function has been revised and updated overtime. Past approaches combined with current powerful technologies provide a more complete picture of the brain’s organization, from how the neurons connect with each other to finer details of every corner inside the neurons.
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Background Intermittent fasting or calorie restriction (CR) diets provide anti-inflammatory and neuroprotective advantages in models of multiple sclerosis (MS); data in humans are sparse. Methods We conducted a randomised-controlled feeding study of different CR diets in 36 people with MS over 8 weeks. Participants were randomised to 1 of 3 diets:...
Article
Extracellular vesicles (EVs) are cell-derived nanoparticles with an important role in intercellular communication, even across brain barriers. The bidirectional brain-barrier crossing capacity of EVs is supported by research identifying neuronal markers in peripheral EVs, as well as the brain delivery of peripherally administered EVs. In addition,...
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Structural alterations or quantitative abnormalities of some mitochondrial ion channels and exchangers are associated with altered neuronal functions and increased susceptibility to mental illness. Here we have assessed levels of functionally prominent mitochondrial calcium ion channel proteins in plasma neuron‐derived extracellular vesicles (NDEVs...
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Besides motor symptoms, many individuals with Parkinson’s disease develop cognitive impairment perhaps due to co-existing α-synuclein and Alzheimer’s disease pathologies and impaired brain insulin signaling. Discovering biomarkers for cognitive impairment in Parkinson’s disease could help clarify the underlying pathogenic processes and improve Park...
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Background Mitochondrial dysfunction plays an important role in multiple sclerosis (MS) disease progression. Plasma extracellular vesicles are a potential source of novel biomarkers in MS, and some of these are derived from mitochondria and contain functional mitochondrial components. Objective To evaluate the relationship between levels of mitoch...
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We investigated whether pupil size can variate with the intensity of cognitive processing in patients with behavioral-variant-Frontotemporal-Dementia (bvFTD). We invited five bvFTD participants and 21 controls to perform forward spans and backward spans, and, in a control condition, to count aloud. We recorded pupil activity using eye-tracking-glas...
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Background Alzheimer’s Disease (AD) is an age-related neurodegenerative disease with a poorly understood etiology, shown to be partly genetic. Glucose hypometabolism, extracellular Amyloid-beta (Aβ) deposition, and intracellular Tau deposition are cardinal features of AD and display characteristic spatial patterns in the brain. We hypothesize that...
Preprint
Full-text available
Most approaches to extracellular vesicle (EV) characterization are size based and provide few clues regarding EV origin, composition, and function. New methods to define EV surface proteins may aid understanding of their origin, physiological role, and biomarker potential. Recently developed highly sensitive immunoassays for intact EV using ELISA,...
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Background and aims Autobiographical memory serves to recall past personal experiences and share them with others, promoting social bonding and communication. In this study, we investigated whether encouraging patients with Alzheimer’s disease (AD) to share autobiographical memories during formal neuropsychological testing may boost the patient–cli...
Preprint
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The immunoaffinity isolation of neuron-derived extracellular vesicles (NDEVs) from blood by targeting the neuronal protein L1CAM has been widely adopted to provide peripheral biomarkers for brain disorders. However, compelling evidence for the presence of L1CAM on NDEVs at the single-EV level has been missing. Here, we demonstrate that L1CAM co-loc...
Article
Patients with major depression (MD) are at high-risk for insulin resistance (IR), type-2 diabetes, metabolic syndrome, cardiovascular morbidity and mortality. However, our recent study published in this journal [Eur Arch Psychiatry Clin Neurosci. 2019 Jun;269(4):373-377], found no evidence of IR in acutely-ill drug-naive first-episode MD (FEMD) usi...
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While visiting and socialization restrictions during lockdowns were instituted to cope with the Covid-19 spread and to prolong the life of residents of retirement homes, these measures could have been expected to decrease the quality of life of their residents. We assessed longitudinal effects of the two successive lockdowns, as implemented in Fran...
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Background Sporadic Alzheimer’s disease (sAD) lacks a unifying hypothesis that can account for the lipid peroxidation observed early in the disease, enrichment of ApoE in the core of neuritic plaques, hallmark plaques and tangles, and selective vulnerability of entorhinal-hippocampal structures. Objective We hypothesized that 1) high expression of...
Article
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Background: Diagnosis of Alzheimer disease (AD) can cause substantial psychological distress in patients. We thus assessed how patients with AD remember the announcement of diagnosis. Methods: We recruited 47 participants with mild AD (26 women; M age=68.89 y, SD=7.37; M years of formal education=9.74, SD=3.00). We invited the participants to re...
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The hallmarks of Alzheimer’s disease (AD) pathology are senile plaques containing amyloid-beta (Aβ) and neurofibrillary tangles containing hyperphosphorylated tau. Additional pathologies often co-exist, whereas multiple pathogenic mechanisms are involved in AD, especially synaptic degeneration, which necessitate the need for synaptic integrity-rela...
Preprint
Full-text available
Background: Intermittent fasting or calorie restriction (CR) diets provide anti-inflammatory and neuroprotective advantages in models of multiple sclerosis (MS); data in humans are sparse. Methods: We conducted a randomized-controlled feeding study of different CR diets in 36 people with MS over 8 weeks. Patients were randomized to receive either:...
Preprint
Most approaches to extracellular vesicle (EV) characterization focus on EV size or density. However, such approaches provide few clues regarding EV origin, molecular composition, and function. New methods to characterize the EV surface proteins may aid our understanding of their origin, physiological roles, and biomarker potential. Recently develop...
Article
Background: Ketone bodies have been proposed as an "energy rescue" for the Alzheimer's disease (AD) brain, which underutilizes glucose. Prior research has shown that oral ketone monoester (KME) safely induces robust ketosis in humans and has demonstrated cognitive-enhancing and pathology-reducing properties in animal models of AD. However, human ev...
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To characterize neuronal mitochondrial abnormalities in major depressive disorder (MDD), functional mitochondrial proteins (MPs) extracted from enriched plasma neuron-derived extracellular vesicles (NDEVs) of MDD participants (n = 20) were quantified before and after eight weeks of treatment with a selective serotonin reuptake inhibitor (SSRI). Pre...
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Mitochondria provide energy to neurons through oxidative phosphorylation and eliminate Reactive Oxygen Species (ROS) through Superoxide Dismutase 1 (SOD1). Dysfunctional mitochondria, manifesting decreased activity of electron transport chain (ETC) complexes and high ROS levels, are involved in Alzheimer’s disease (AD) pathogenesis. We hypothesized...
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Background Irritable bowel syndrome (IBS) is characterized by abdominal pain, bowel habit alterations, and psychiatric comorbidities. Although pathophysiology remains incompletely understood, prior work demonstrates associations with brain‐derived neurotrophic factor (BDNF) and catechol‐O‐methyltransferase (COMT). The purpose of this study was to q...
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Background In a previous study, we assessed burnout in geriatric healthcare workers during the first lockdown that lasted from March to May 2020 in France, in response to the COVID-19 crisis. Objective We carried out a follow-up study to assess burnout in the same population during the second lockdown that was implemented at the end of October 202...
Preprint
Full-text available
Background Sporadic Alzheimer’s disease (sAD) lacks a unifying hypothesis that can account for the lipid peroxidation observed early in the disease, enrichment of ApoE in the central core of neuritic plaques, the hallmark plaques and tangles, and the selective vulnerability of entorhinal-hippocampal structures. Objective We hypothesized that (1) h...
Article
Full-text available
We identified biologically relevant moderators of response to tumor necrosis factor (TNF)-α inhibitor, infliximab, among 60 individuals with bipolar depression. Data were derived from a 12-week, randomized, placebo-controlled clinical trial secondarily evaluating the efficacy of infliximab on a measure of anhedonia (i.e., Snaith–Hamilton Pleasure S...
Article
Background Atrial fibrillation (AF) is a risk factor for cognitive impairment and dementia in patients with stroke history. However, the association between AF and cognitive impairment in broader populations is less clear.Objective To systematically review and quantitatively synthesize the existing evidence regarding the association of AF with cogn...
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There is substantial experimental evidence for dysregulation of several microRNA (miRNA) expression levels in Alzheimer’s disease (AD). MiRNAs modulate critical brain intracellular signaling pathways and are associated with AD core pathophysiological mechanisms. First, we conducted a real-time quantitative PCR-based pilot study to identify a set of...
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Invaginating structures are common in the synapses of most animals. However, the details of these invaginating structures remain understudied in part because they are not well resolved in light microscopy and were often misidentified in early electron microscope (EM) studies. Utilizing experimental techniques along with the latest advances in micro...
Preprint
BACKGROUND In a previous study, we assessed burnout in geriatric healthcare workers during the first lockdown that lasted from March to May 2020 in France, in response to the Covid-19 crisis. OBJECTIVE We carried out a follow-up study to assess burnout in the same population during the second lockdown that was implemented at the end of October 202...
Article
Full-text available
Circulating neuronal extracellular vesicles (NEVs) of Alzheimer’s disease (AD) patients show high Tau and β-amyloid (Aβ) levels, whereas their astrocytic EVs (AEVs) contain high complement levels. To validate EV proteins as AD biomarkers, we immunocaptured NEVs and AEVs from plasma collected from fifteen wild type (WT), four 2xTg-AD, nine 5xFAD, an...
Article
Objective To investigate the effects of monoclonal antibodies against Aβ on cognition, function, amyloid PET and other biomarkers, as well as risk for amyloid-related imaging abnormalities (ARIA) and other adverse events, in Alzheimer’s disease (AD). Methods Pubmed, Web of Science, ClinicalTrials.gov and gray literature were searched for phase III...
Article
Accumulating evidence suggests that disrupted insulin signaling is involved in bipolar disorder (BD) pathogenesis. Herein, we aimed to directly explore the potential role of neuronal insulin signaling using an innovative technique based on biomarkers derived from plasma extracellular vesicles enriched for neuronal origin (NEVs). We leveraged plasma...
Article
We used plasma neuronal extracellular vesicles to examine how neuronal insulin signaling proteins relate cross-sectionally to brain structure in nondemented older adults with varying levels of cortical amyloid. Extracellular vesicles enriched for neuronal origin by anti-L1CAM immunoabsorption were isolated from plasma of Atherosclerosis Risk in Com...
Chapter
Precision medicine, also known as personalized medicine, is concerned with finding the right treatment for the right patient at the right time. It is a way of thinking focused on parsing heterogeneity ultimately down to the level of the individual. Its main mission is to identify characteristics of heterogeneous clinical conditions so as to target...
Article
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Chronic inflammation is thought to contribute to the early pathogenesis of Alzheimer's disease (AD). However, the precise mechanism by which inflammatory cytokines promote the formation and deposition of Aβ remains unclear. Available data suggest that applications of inflammatory cytokines onto isolated neurons do not promote the formation of Aβ, s...
Article
Background Circulating neuronal and astrocytic Extracellular Vesicles (NEVs, AEVs) provide biomarkers for Alzheimer’s disease (AD) (including total and p‐Tau in NEVs, complement in AEVs). In a large case‐control study leveraging Baltimore Longitudinal Study of Aging samples, Tau‐related NEV biomarkers predicted future AD diagnosis with high accurac...
Article
Neuroinflammation, a key early pathomechanistic alteration of Alzheimer's disease, may represent either a detrimental or a compensatory mechanism or both (according to the disease stage). YKL-40, a glycoprotein highly expressed in differentiated glial cells, is a candidate biomarker for in vivo tracking neuroinflammation in humans. We performed a l...
Article
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Alzheimer’s disease (AD) is the most common type of dementia. Amyloid β (Aβ) plaques, tau-containing neurofibrillary tangles, and neuronal loss leading to brain atrophy are pathologic hallmarks of AD. Given the importance of early diagnosis, extensive efforts have been undertaken to identify diagnostic and prognostic biomarkers for AD. Circulating...
Article
Full-text available
Introduction: This study investigated the effect of pictorial cues on autobiographical memory in Alzheimer's disease (AD). We assessed autobiographical memory of patients with AD and cognitively normal older adults in two conditions. Methods: In one condition, the participants were provided with verbal instructions to retrieve three autobiograph...
Article
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β-Secretase1 (BACE1) protein concentrations and rates of enzyme activity, analyzed in human bodily fluids, are promising candidate biological markers for guidance in clinical trials investigating BACE1 inhibitors to halt or delay the dysregulation of the amyloid-β pathway in Alzheimer's disease (AD). A robust body of evidence demonstrates an associ...
Article
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Background/Objective The COVID-19 crisis has been increasing the burden of healthcare workers in acute care geriatric facilities. These workers have been dealing with drastic changes in the care they provide to their residents including cancelation of group activities and communal dining and even restrictions of activities outside rooms. Healthcare...
Article
Full-text available
Traumatic brain injury (TBI) is a serious global health concern, many individuals live with TBI-related neurological dysfunction. A lack of biomarkers of TBI has impeded medication development. To identify new potential biomarkers, we time-dependently evaluated mouse brain tissue and neuronally derived plasma extracellular vesicles proteins in a mi...
Article
Full-text available
Traumatic brain injury (TBI) is a serious global health problem, many individuals live with TBI-related neurological dysfunction. A lack of biomarkers of TBI has impeded medication development. To identify new potential biomarkers, we time-dependently evaluated mouse brain tissue and neuronally derived plasma extracellular vesicle proteins in a mil...
Article
Full-text available
Traumatic brain injury (TBI) is a serious global health problem, many individuals live with TBI-related neurological dysfunction. A lack of biomarkers of TBI has impeded medication development. To identify new potential biomarkers, we time-dependently evaluated mouse brain tissue and neuronally derived plasma extracellular vesicle proteins in a mil...
Article
Full-text available
Mitochondrial function relies on multiple quality control mechanisms, including the release of mitochondrial vesicles. To investigate the ultrastructure and prevalence of mitochondrial membranous protrusions (and, by extension, vesicles) in neurons, we surveyed mitochondria in rat and planarian brains using transmission electron microscopy (EM). We...
Chapter
To meet its high energy demands, the brain mostly utilizes glucose. However, the brain has evolved to exploit additional fuels, such as ketones, especially during prolonged fasting. With aging and neurodegenerative diseases (NDDs), the brain becomes inefficient at utilizing glucose due to changes in glia and neurons that involve glucose transport,...
Article
Full-text available
We have previously shown that blood astrocytic-origin extracellular vesicles (AEVs) from Alzheimer’s disease (AD) patients contain high complement levels. To test the hypothesis that circulating EVs from AD patients can induce complement-mediated neurotoxicity involving Membrane Attack Complex (MAC) formation, we assessed the effects of immunocaptu...

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