ApoE ε4-dependent alteration of CXCR3 CD127 CD4 T cells is associated with elevated plasma neurofilament light chain in Alzheimer's disease.

Unlabelled: Recent findings indicate a correlation between the peripheral adaptive immune system and neuroinflammation in Alzheimer's disease (AD). To characterize the composition of adaptive immune cells in the peripheral blood of AD patients, we utilized single-cell mass cytometry (CyTOF) to profile peripheral blood mononuclear cells (PBMCs). Concurrently, we assessed the concentration of proteins associated with AD and neuroinflammation in the plasma of the same subjects.

Prevalence of Mild Cognitive Impairment and Alzheimer's Disease Identified in Veterans in the United States.

Background: Diagnostic codes can be instrumental for case identification in Alzheimer's disease (AD) research; however, this method has known limitations and cannot distinguish between disease stages. Clinical notes may offer more detailed information including AD severity and can complement diagnostic codes for case identification.

Objective: To estimate prevalence of mild cognitive impairment (MCI) and AD using diagnostics codes and clinical notes available in the electronic healthcare record (EHR).

Clinical Characterization of Veterans With Alzheimer Disease by Disease Severity in the United States.

Purpose: We aimed to examine the clinical characteristics of US veterans who underwent neurocognitive test score-based assessments of Alzheimer disease (AD) stage in the Veterans Affairs Healthcare System (VAHS).

Methods: Test dates for specific stages of AD were referenced as index dates to study behavioral and psychological symptoms of dementia (BPSD) and other patient characteristics related to utilization/work-up and time to death.

Patients: We identified veterans with AD and neurocognitive evaluations using the VAHS Electronic Health Record (EHR).

Effect of the ROCK inhibitor fasudil on the brain proteomic profile in the tau transgenic mouse model of Alzheimer's disease.

Introduction: The goal of this study is to explore the pharmacological potential of the amyloid-reducing vasodilator fasudil, a selective Ras homolog (Rho)-associated kinases (ROCK) inhibitor, in the P301S tau transgenic mouse model (Line PS19) of neurodegenerative tauopathy and Alzheimer's disease (AD).

Methods: We used LC-MS/MS, ELISA and bioinformatic approaches to investigate the effect of treatment with fasudil on the brain proteomic profile in PS19 tau transgenic mice. We also explored the efficacy of fasudil in reducing tau phosphorylation, and the potential beneficial and/or toxic effects of its administration in mice.

Alzheimer's Disease Stage Transitions Among United States Veterans.

Background: Alzheimer's disease (AD) and related dementias are progressive neurological disorders with stage-specific clinical features and challenges. An important knowledge gap is the "window of time" within which patients transition from mild cognitive impairment or mild AD to moderate or severe AD. Better characterization/establishment of transition times would help clinicians initiating treatments, including anti-amyloid therapy.

Reduction of Phosphorylated Tau in Alzheimer's Disease Induced Pluripotent Stem Cell-Derived Neuro-Spheroids by Rho-Associated Coiled-Coil Kinase Inhibitor Fasudil.

Background: Alzheimer's disease (AD) is the most predominant form of dementia. Rho-associated coiled coil kinase (ROCK) inhibitor, fasudil, is one of the candidate drugs against the AD progression.

Objective: We aimed to investigate possible changes of AD associated markers in three-dimensional neuro-spheroids (3D neuro-spheroids) generated from induced pluripotent stem cells derived from AD patients or healthy control subjects (HC) and to determine the impact of pharmacological intervention with the ROCK inhibitor fasudil.

Rule-Based Identification of Individuals with Mild Cognitive Impairment or Alzheimer's Disease Using Clinical Notes from the United States Veterans Affairs Healthcare System.

Background: Early identification of individuals with mild cognitive impairment (MCI) and Alzheimer's disease (AD) is a clinical and research imperative. Use of diagnostic codes for MCI and AD identification has limitations. We used clinical notes to supplement diagnostic codes in the Veterans Affairs Healthcare System (VAHS) electronic health records (EHR) to identify and establish cohorts of Veterans recorded with MCI or AD.

Clinical and Scientific Challenges to Effectiveness Studies Under Coverage with Evidence Development in Alzheimer's Disease.

The Centers for Medicare and Medicaid Services (CMS) has recently issued a national coverage determination for US Food and Drug Administration (FDA)-approved anti-amyloid monoclonal antibodies (mAbs) for the treatment of Alzheimer's disease (AD) under coverage with evidence development (CED). CED schemes are complex, costly, and challenging, and often fail to achieve intended objectives because of administrative and implementation issues. AD is a heterogeneous, progressive neurodegenerative disorder with complex care pathway that additionally presents scientific challenges related to the choice of study design and methods used in evaluating CED schemes.

Clinical Staging of Alzheimer's Disease: Concordance of Subjective and Objective Assessments in the Veteran's Affairs Healthcare System.

Introduction: Uncertainty surrounding the accurate assessment of the early-stage Alzheimer's disease (AD) may cause delayed care and inappropriate patient access to new AD therapies.

Methods: To analyze clinical assessments of patients with AD in the Veteran's Affairs (VA) Healthcare System and evaluate concordance between subjective and objective assessments, we processed clinical notes extracted by text integration utilities between April 1, 2008 and October 14, 2021. Veterans who had mild, moderate, or severe AD with clinical notes documenting both clinician's judgement of AD severity and objective test scores from the Mini-Mental State Examination or the Montreal Cognitive Assessment were included.

Historical contingency and the role of post-invasion evolution in alternative community states.

Historical contingency has long figured prominently in the conceptual frameworks of evolutionary biology and community ecology. Evolutionary biologists typically consider the effects of chance mutation and historical contingency in driving divergence and convergence of traits in populations, whereas ecologists instead are often interested in the role of historical contingency in community assembly and succession. Although genetic differences among individuals in populations can influence community interactions, variability among populations of the same species has received relatively little attention for its potential role in community assembly and succession.

Network topology and patch connectivity affect dynamics in experimental and model metapopulations.

Biological populations are rarely isolated in space and instead interact with others via dispersal in metapopulations. Theory predicts that network connectivity patterns can have critical effects on network robustness, as certain topologies, such as scale-free networks, are more tolerant to disturbances than other patterns. However, at present, experimental evidence of how these topologies affect population dynamics in a metapopulation framework is lacking.

Using Video Telehealth to Deliver Patient-Centered Collaborative Care: The G-IMPACT Pilot.

: This pilot project aimed to explore a new model of healthcare delivery to older adult medically complex Veterans by combining telehealth technology with an interdisciplinary medical team operating in real time.: The Geriatric-Interdisciplinary Mobile Patient Access Team (G-IMPACT) was comprised of a field team including a nurse practitioner and technology assistant who visited enrolled patients in their homes using synchronous video to link to a suite of geriatric specialists in a video-enabled room at a Veterans Affairs hospital. Clinicians interacted with patients, caregivers, and each other to develop mutually agreed upon treatment plans that were then immediately implemented in the field.

Evolution alters post-invasion temporal dynamics in experimental communities.

The causes and consequences of temporal variation in the abundance of organisms constitute central themes in ecological inquiry. Rapid evolution can occur over ecological time-scales, potentially resulting in altered temporal variation in abundance and complicating inferences about the consequences of temporal variation. We assessed whether evolution altered the temporal variability in species' abundances in simple assemblages of species.

A role for APP in Wnt signalling links synapse loss with β-amyloid production.

In Alzheimer's disease (AD), the canonical Wnt inhibitor Dickkopf-1 (Dkk1) is induced by β-amyloid (Aβ) and shifts the balance from canonical towards non-canonical Wnt signalling. Canonical (Wnt-β-catenin) signalling promotes synapse stability, while non-canonical (Wnt-PCP) signalling favours synapse retraction; thus Aβ-driven synapse loss is mediated by Dkk1. Here we show that the Amyloid Precursor Protein (APP) co-activates both arms of Wnt signalling through physical interactions with Wnt co-receptors LRP6 and Vangl2, to bi-directionally modulate synapse stability.

Amyloid β synaptotoxicity is Wnt-PCP dependent and blocked by fasudil.

Introduction: Synapse loss is the structural correlate of the cognitive decline indicative of dementia. In the brains of Alzheimer's disease sufferers, amyloid β (Aβ) peptides aggregate to form senile plaques but as soluble peptides are toxic to synapses. We previously demonstrated that Aβ induces Dickkopf-1 (Dkk1), which in turn activates the Wnt-planar cell polarity (Wnt-PCP) pathway to drive tau pathology and neuronal death.

Evolution alters the consequences of invasions in experimental communities.

Evolution has the capacity to alter the course of biological invasions, although such changes remain mostly unexplored by experiments. Integrating evolution into studies of invasions is important, because species traits can potentially evolve in ways that either moderate or exacerbate the impacts of invasions. We have assessed whether species evolved during experimental invasions by comparing the performance of founder populations and their potentially evolved descendants in communities of ciliates and rotifers.

Pervasive interactions between foliar microbes and soil nutrients mediate leaf production and herbivore damage in a tropical forest.

Producing and retaining leaves underlie the performance and survivorship of seedlings in deeply shaded tropical forests. These habitats are characterized by conditions ideal for foliar bacteria, which can be potent plant pathogens. Leaf production, retention and susceptibility to enemies may ultimately depend upon interactions among soil nutrients and foliar microbes, yet this has never been tested.

Sortilin and retromer mediate retrograde transport of Glut4 in 3T3-L1 adipocytes.

Sortilin is a multiligand sorting receptor responsible for the anterograde transport of lysosomal enzymes and substrates. Here we demonstrate that sortilin is also involved in retrograde protein traffic. In cultured 3T3-L1 adipocytes, sortilin together with retromer rescues Glut4 from degradation in lysosomes and retrieves it to the TGN, where insulin--responsive vesicles are formed.

Influences of Host Community Characteristics on Borrelia burgdorferi Infection Prevalence in Blacklegged Ticks.

Lyme disease is a major vector-borne bacterial disease in the USA. The disease is caused by Borrelia burgdorferi, and transmitted among hosts and humans, primarily by blacklegged ticks (Ixodes scapularis). The ~25 B.

Foliar bacteria and soil fertility mediate seedling performance: a new and cryptic dimension of niche differentiation.

The phyllosphere (comprising the leaf surface and interior) is one of the world's largest microbial habitats and is host to an abundant and diverse array of bacteria. Nonetheless, the degree to which bacterial communities are benign, harmful, or beneficial to plants in situ is unknown. We tested the hypothesis that the net effect of reducing bacterial abundance and diversity would vary substantially among host species (from harmful to beneficial) and this would be strongly mediated by soil resource availability.

Three Dimensional Human Neuro-Spheroid Model of Alzheimer's Disease Based on Differentiated Induced Pluripotent Stem Cells.

The testing of candidate drugs to slow progression of Alzheimer's disease (AD) requires clinical trials that are lengthy and expensive. Efforts to model the biochemical milieu of the AD brain may be greatly facilitated by combining two cutting edge technologies to generate three-dimensional (3D) human neuro-spheroid from induced pluripotent stem cells (iPSC) derived from AD subjects. We created iPSC from blood cells of five AD patients and differentiated them into 3D human neuronal culture.

Peripheral blood mononuclear cell-converted induced pluripotent stem cells (iPSCs) from an early onset Alzheimer's patient.

Improvement in transduction efficiency makes it possible to convert blood cells into induced pluripotent stem cells (iPSC). In this study, we generated an iPSC line from peripheral blood mononuclear cells (PBMC) donated by a patient who exhibited memory deficit at age 59; outcome of positron emission tomography scan is consistent with a diagnosis of Alzheimer's disease. Integration-free CytoTune-iPS Sendai Reprogramming factors which include Sendai virus particles of the four Yamanaka factors Oct4, Sox2, Klf4, and c-Myc were introduced to PBMC to convert them to iPSCs without retention of virus.

Induced pluripotent stem cells (iPSCs) derived from frontotemporal dementia patient's peripheral blood mononuclear cells.

Peripheral blood mononuclear cells (PBMC) were donated by a patient with clinically diagnosed frontotemporal dementia (FTD). Induced pluripotent stem cells (iPSCs) were developed using integration-free CytoTune-iPS Sendai Reprogramming factors which include Sendai virus particles of the four Yamanaka factors Oct, Sox2, Klf4, and c-Myc.

Home-Based Video Telehealth for Veterans With Dementia.

In-home video telehealth supplements office visits and offers comfort and convenience to patients with dementia and their caregivers.