608 results match your criteria: "Institute for Memory Impairments and Neurological Disorders[Affiliation]"

Background: This study extends prior research from the MRI substudy of the Women's Health Initiative Memory Study (WHIMS-MRI) linking BMI to reduced brain atrophy and ischemic lesion load by examining DXA-based measurements of total body fat, total abdominal adipose tissue (TAT), abdominal visceral (VAT) and subcutaneous (SAT) adipose tissue, gynoid fat, and overall leg fat.

Methods: The analytic sample consisted of 61 postmenopausal women (baseline mean age 69.5 [3.

View Article and Find Full Text PDF

The R47H missense mutation of the TREM2 gene is a known risk factor for development of Alzheimer's Disease. In this study, we analyze the impact of the Trem2 mutation on specific cell types in multiple cortical and subcortical brain regions in the context of wild-type and 5xFAD mouse background. We profile 19 mouse brain sections consisting of wild-type, Trem2, 5xFAD and Trem2; 5xFAD genotypes using MERFISH spatial transcriptomics, a technique that enables subcellular profiling of spatial gene expression.

View Article and Find Full Text PDF
Article Synopsis
  • The study investigates recruitment challenges faced by decision-makers for individuals with and without Down syndrome (DS), emphasizing the need to understand differing research attitudes to avoid sample bias.* ! -
  • Using data from two registries, the study compares Research Attitudes Questionnaire (RAQ) scores between non-DS decision-makers and family decision-makers of individuals with DS.* ! -
  • Although overall RAQ scores were similar, the study found that DS decision-makers expressed a greater sense of responsibility to help others but were less optimistic about medical research curing major diseases in their lifetime.* !
View Article and Find Full Text PDF

Understanding the normal function of the Huntingtin (HTT) protein is of significance in the design and implementation of therapeutic strategies for Huntington's disease (HD). Expansion of the CAG repeat in the gene, encoding an expanded polyglutamine (polyQ) repeat within the HTT protein, causes HD and may compromise HTT's normal activity contributing to HD pathology. Here, we investigated the previously defined role of HTT in autophagy specifically through studying HTT's association with ubiquitin.

View Article and Find Full Text PDF

The utility of recruitment incentives in early Alzheimer's disease trials.

Alzheimers Dement

September 2024

UC Irvine Institute for Memory Impairments and Neurological Disorders, University of California, Irvine, California, USA.

Introduction: Amid recent approvals, early Alzheimer's disease (AD) remains an active area of treatment development.

Methods: We performed a conjoint experiment to compare preferences among 26 patients with mild cognitive impairment for four trial features including designs incorporating active aducanumab-control (vs. placebo), returning tau positron emission tomography (PET) results (vs.

View Article and Find Full Text PDF

Introduction: Understanding attitudes toward participation among diverse preclinical Alzheimer's disease (AD) trial participants could yield insights to instruct future recruitment.

Methods: Using data from the Anti-Amyloid Treatment in Asymptomatic AD (A4) Study, we examined differences among mutually exclusive racial and ethnic groups in views and perceptions of amyloid imaging (VPAI), a measure of motivations to undergo amyloid biomarker testing in the setting of preclinical AD. We used linear regression to quantify differences at baseline.

View Article and Find Full Text PDF

Circuit dynamics of the olfactory pathway during olfactory learning.

Front Neural Circuits

July 2024

Department of Anatomy and Neurobiology, School of Medicine, University of California, Irvine, Irvine, United States.

The olfactory system plays crucial roles in perceiving and interacting with their surroundings. Previous studies have deciphered basic odor perceptions, but how information processing in the olfactory system is associated with learning and memory is poorly understood. In this review, we summarize recent studies on the anatomy and functional dynamics of the mouse olfactory learning pathway, focusing on how neuronal circuits in the olfactory bulb (OB) and olfactory cortical areas integrate odor information in learning.

View Article and Find Full Text PDF

Microglia, the immune cells of the central nervous system, are dynamic and heterogenous cells. While single cell RNA sequencing has become the conventional methodology for evaluating microglial state, transcriptomics do not provide insight into functional changes, identifying a critical gap in the field. Here, we propose a novel organelle phenotyping approach in which we treat live human induced pluripotent stem cell-derived microglia (iMGL) with organelle dyes staining mitochondria, lipids, lysosomes and acquire data by live-cell spectral microscopy.

View Article and Find Full Text PDF

Centers for Medicare and Medicaid Services Coverage of Amyloid PET.

JAMA Neurol

September 2024

Department of Health and Community Systems, University of Pittsburgh School of Nursing, University of Pittsburgh Alzheimer's Disease Research Center, UPMC Montefiore, Pittsburgh, Pennsylvania.

View Article and Find Full Text PDF

Lipid changes in the brain have been implicated in many neurodegenerative diseases including Alzheimer's Disease (AD), Parkinson's disease and Amyotrophic Lateral Sclerosis. To facilitate comparative lipidomic research across brain-diseases we established a data commons named the Neurolipid Atlas, that we have pre-populated with novel human, mouse and isogenic induced pluripotent stem cell (iPSC)-derived lipidomics data for different brain diseases. We show that iPSC-derived neurons, microglia and astrocytes display distinct lipid profiles that recapitulate lipotypes.

View Article and Find Full Text PDF

The central nervous system (CNS) is constantly surveilled by microglia, highly motile and dynamic cells deputed to act as the first line of immune defense in the brain and spinal cord. Alterations in the homeostasis of the CNS are detected by microglia that respond by extending their processes or - following major injuries - by migrating toward the affected area. Understanding the mechanisms controlling directed cell migration of microglia is crucial to dissect their responses to neuroinflammation and injury.

View Article and Find Full Text PDF

APOE4 is the strongest genetic risk factor for Alzheimer's disease (AD), with increased odds ratios in female carriers. Targeting amyloid plaques shows modest improvement in male non-APOE4 carriers. Leveraging single-cell transcriptomics across APOE variants in both sexes, multiplex flow cytometry and validation in two independent cohorts of APOE4 female carriers with AD, we identify a new subset of neutrophils interacting with microglia associated with cognitive impairment.

View Article and Find Full Text PDF
Article Synopsis
  • The urgent global challenge of Alzheimer's Disease (AD) highlights the need for innovative treatments, particularly as current options remain limited in effectiveness.
  • Research is focusing on immunotherapies, like the FDA-approved lecanemab, which shows promise in reducing harmful brain aggregates, though benefits so far have been modest.
  • A new universal vaccine platform, MultiTEP, has been developed, leading to the initiation of clinical trials for a DNA vaccine (AV-1959D) and a novel mRNA vaccine (AV-1959LR), which are showing promising initial immunogenicity results in animal studies.
View Article and Find Full Text PDF

Within the last two decades, SARS-CoV-2 was the third zoonotic severe acute respiratory betacoronavirus (sarbecovirus) to infect humans, following SARS and MERS. The disruptions caused by the pandemic underscore the need for a universal vaccine against respiratory betacoronaviruses. Our group previously developed the universal platform for vaccine development, MultiTEP, which has been utilized in this study to generate a range of SARS-CoV-2 epitope vaccine candidates.

View Article and Find Full Text PDF

Central nervous system (CNS) lesions become surrounded by neuroprotective borders of newly proliferated reactive astrocytes; however, fundamental features of these cells are poorly understood. Here we show that following spinal cord injury or stroke, 90% and 10% of border-forming astrocytes derive, respectively, from proliferating local astrocytes and oligodendrocyte progenitor cells in adult mice of both sexes. Temporal transcriptome analysis, single-nucleus RNA sequencing and immunohistochemistry show that after focal CNS injury, local mature astrocytes dedifferentiate, proliferate and become transcriptionally reprogrammed to permanently altered new states, with persisting downregulation of molecules associated with astrocyte-neuron interactions and upregulation of molecules associated with wound healing, microbial defense and interactions with stromal and immune cells.

View Article and Find Full Text PDF

The impact of astrocytic NF-κB on healthy and Alzheimer's disease brains.

Sci Rep

June 2024

Clem Jones Centre for Ageing Dementia Research, Queensland Brain Institute, The University of Queensland, Brisbane, QLD, Australia.

Astrocytes play a role in healthy cognitive function and Alzheimer's disease (AD). The transcriptional factor nuclear factor-κB (NF-κB) drives astrocyte diversity, but the mechanisms are not fully understood. By combining studies in human brains and animal models and selectively manipulating NF-κB function in astrocytes, we deepened the understanding of the role of astrocytic NF-κB in brain health and AD.

View Article and Find Full Text PDF

Therapeutic potential of human microglia transplantation in a chimeric model of CSF1R-related leukoencephalopathy.

Neuron

August 2024

Department of Neurobiology & Behavior, University of California, Irvine, Irvine, CA, USA; Institute for Memory Impairments and Neurological Disorders, University of California, Irvine, Irvine, CA, USA; Sue and Bill Gross Stem Cell Research Center, University of California, Irvine, Irvine, CA, USA. Electronic address:

Microglia replacement strategies are increasingly being considered for the treatment of primary microgliopathies like adult-onset leukoencephalopathy with axonal spheroids and pigmented glia (ALSP). However, available mouse models fail to recapitulate the diverse neuropathologies and reduced microglia numbers observed in patients. In this study, we generated a xenotolerant mouse model lacking the fms-intronic regulatory element (FIRE) enhancer within Csf1r, which develops nearly all the hallmark pathologies associated with ALSP.

View Article and Find Full Text PDF

Microglia protect against age-associated brain pathologies.

Neuron

August 2024

UK Dementia Research Institute at the University of Edinburgh, Edinburgh Medical School, Chancellor's Building, Edinburgh EH16 4SB, UK; Centre for Clinical Brain Sciences, University of Edinburgh, Chancellor's Building, 49 Little France Crescent, Edinburgh EH16 4SB, UK; Department of Psychiatry and Psychotherapy, School of Medicine and Health, Klinikum rechts der Isar, Technical University Munich, and German Center for Mental Health (DZPG), 81675 Munich, Germany; Neuropsychiatry and Laboratory of Molecular Psychiatry, Charité - Universitätsmedizin Berlin and DZNE, 10117 Berlin, Germany. Electronic address:

Microglia are brain-resident macrophages that contribute to central nervous system (CNS) development, maturation, and preservation. Here, we examine the consequences of permanent microglial deficiencies on brain aging using the Csf1r mouse model. In juvenile Csf1r mice, we show that microglia are dispensable for the transcriptomic maturation of other brain cell types.

View Article and Find Full Text PDF

TDP-43 proteinopathy is a salient neuropathologic feature in a subset of frontotemporal lobar degeneration (FTLD-TDP), in amyotrophic lateral sclerosis (ALS-TDP), and in limbic-predominant age-related TDP-43 encephalopathy neuropathologic change (LATE-NC), and is associated with hippocampal sclerosis of aging (HS-A). We examined TDP-43-related pathology data in the National Alzheimer's Coordinating Center (NACC) in two parts: (I) availability of assessments, and (II) associations with clinical diagnoses and other neuropathologies in those with all TDP-43 measures available. Part I: Of 4326 participants with neuropathology data collected using forms that included TDP-43 assessments, data availability was highest for HS-A (97%) and ALS (94%), followed by FTLD-TDP (83%).

View Article and Find Full Text PDF

Background: Apolipoprotein E ε4 (APOE4) is the strongest genetic risk factor for late-onset Alzheimer's disease (LOAD). A recent case report identified a rare variant in APOE, APOE3-R136S (Christchurch), proposed to confer resistance to autosomal dominant Alzheimer's Disease (AD). However, it remains unclear whether and how this variant exerts its protective effects.

View Article and Find Full Text PDF
Article Synopsis
  • A study investigates the relationship between obstructive sleep apnea (OSA) and insomnia symptoms with Alzheimer's disease (AD) in adults with Down syndrome (DS), highlighting the need for more research in this area.
  • Findings show that older women with DS who have dementia experience more severe insomnia symptoms compared to those without dementia, but OSA symptoms do not differ significantly.
  • The results suggest that treating insomnia symptoms could be crucial for improving daily living activities and slowing the progression of dementia in adults with DS.
View Article and Find Full Text PDF

The high heritability of amyotrophic lateral sclerosis (ALS) contrasts with its low molecular diagnosis rate post-genetic testing, pointing to potential undiscovered genetic factors. To aid the exploration of these factors, we introduced EpiOut, an algorithm to identify chromatin accessibility outliers that are regions exhibiting divergent accessibility from the population baseline in a single or few samples. Annotation of accessible regions with histone chromatin immunoprecipitation sequencing and Hi-C indicates that outliers are concentrated in functional loci, especially among promoters interacting with active enhancers.

View Article and Find Full Text PDF

Unlabelled: Japanese encephalitis virus (JEV), a member of the Flaviviridae family, is a leading cause of viral encephalitis in humans. Survivors of this infection often develop lifelong neurological sequelae. Short-chain fatty acids (SCFAs) produced in the gut are vital mediators of the gut-brain axis.

View Article and Find Full Text PDF

Facioscapulohumeral muscular dystrophy (FSHD) is linked to abnormal derepression of the transcription activator DUX4. This effect is localized to a low percentage of cells, requiring single-cell analysis. However, single-cell/nucleus RNA-seq cannot fully capture the transcriptome of multinucleated large myotubes.

View Article and Find Full Text PDF

Background: Higher allostatic load (AL), a multi-system measure of physiological dysregulation considered a proxy for chronic stress exposure, is associated with poorer global cognition (GC) in older non-Hispanic white adults. However, evidence of these associations in middle-aged and older US-based Hispanic/Latino adults is limited.

Objective: To examine associations of AL with level of cognition, performance in cognition 7 years later, and change in cognition over 7 years among middle-aged and older US-based Hispanic/Latino adults.

View Article and Find Full Text PDF