The association between SLIT2 in human vitreous humor and plasma and neurocognitive test scores.

BackgroundSlit Guidance Ligand 2 (SLIT2) binds Roundabout (ROBO) guidance receptors to direct axon pathfinding and neuron migration during nervous system development. SLIT2 expression has previously been linked to dementia risk.ObjectiveTo study the association between SLIT2 expression in human vitreous humor and plasma samples and neurocognitive test scores in a cross-sectional cohort study utilizing a novel, highly-sensitive Meso Scale Discovery (MSD) assay for SLIT2 detection.

The impact of blood MCP-1 levels on Alzheimer's disease with genetic variation at the NAV3 and UNC5C loci.

Monocyte chemoattractant protein-1 (MCP-1), a cytokine involved in peripheral inflammation, has been shown to modulate established Alzheimer's disease (AD) loci. In this study, we hypothesized that blood MCP-1 levels may impact the associations of other genetic variants with AD risk beyond the well-established AD loci. We performed a genome-wide association study (GWAS) using logistic regression with the generalized estimating equation (GEE) and Cox proportional hazards models to examine the combined effects of single nucleotide polymorphisms (SNPs) and blood MCP-1 levels on AD.

The Association Between Retinal Vascular Occlusions and Dementia: A UK Biobank Retrospective Longitudinal Study.

Purpose: Vascular disease is associated with increased incidence of dementia and has the potential to be an indicator of underlying cognitive disease. The goal of this study is to investigate the association between retinal vascular occlusions and neurodegenerative disorders that lead to dementia, including all-cause dementia, Alzheimer's disease (AD), and vascular dementia (VD).

Design: Retrospective longitudinal cohort study.

Comparison of multiple quantitative strategies for neuropathologic image analyses.

The traditional semiquantitative (SQ) scoring system for neuropathologic assessment, although widely used, is prone to variability among assessors and does not capture the full spectrum of pathological changes. To address these limitations, digital pathology-based strategies like positive pixel quantitation or advanced artificial intelligence (AI) techniques have been developed. However, a comprehensive comparison of these measures has never been performed.

Glial fibrillary acidic protein in plasma and intraocular fluids and the correlation with cognitive function in patients with vitreoretinal disease.

Ocular imaging and fluid protein levels are emerging as biomarkers for neurodegenerative disease. Elevated levels of plasma glial fibrillary acidic protein (GFAP), a marker of astrogliosis, have been demonstrated early in the course of Alzheimer's Disease. In this study, we measured GFAP levels in the aqueous and vitreous humors and plasma of 79 participants undergoing vitrectomy surgery for retinal disease and correlated them with subject Mini Mental Status Exam (MMSE) and Trail Making Test part b (TMT-b) scores.

The Association Between SLIT2 in Human Vitreous Humor and Plasma and Neurocognitive Test Scores.

Background: Slit Guidance Ligand 2 (SLIT2) binds Roundabout (ROBO) guidance receptors to direct axon pathfinding and neuron migration during nervous system development. SLIT2 expression has previously been linked to dementia risk.

Objective: To study the association between SLIT2 expression in human vitreous humor and plasma samples and neurocognitive test scores in a cross-sectional cohort study utilizing a novel, highly-sensitive Meso Scale Discovery (MSD) assay for SLIT2 detection.

NeuID, a novel neuron-specific lncRNA, resolves a key epigenetic mechanism linking gene silencing to Alzheimer's disease.

Unlabelled: The increasing evidence that non-coding RNAs can become deregulated during pathogenesis is dramatically expanding the space for drug discovery beyond the protein-coding genome. Long noncoding RNAs (lncRNAs) are emerging as key regulators of cellular function, yet most remain uncharacterized. Here, we identify a previously unstudied lncRNA, which we named ronal entity ( )-a conserved, brain-enriched transcript expressed exclusively in neurons.

A structural haplotype in the 17q21.31 MAPT region is associated with increased risk for chronic traumatic encephalopathy endophenotypes.

Chronic traumatic encephalopathy (CTE) is a neurodegenerative tauopathy associated with repetitive head impact (RHI) exposure. Genetic variation in the 17q21.31 region, containing microtubule-associated protein tau (MAPT), has been implicated in tauopathies but has not been investigated in CTE.

Sex differences on tau, astrocytic, and neurodegenerative plasma biomarkers.

BackgroundSex differences have consistently been identified on autopsy, neuroimaging, and cerebrospinal fluid outcomes related to Alzheimer's disease (AD), but the exact mechanisms for these associations are unclear. Blood-based biomarkers are practical alternatives for the investigation of mechanisms of AD, in addition to accurate disease detection and monitoring.ObjectiveThe objective of this study was to examine sex differences across a panel of blood-based plasma biomarkers in participants with and without cognitive impairment due to AD.

Does white matter and vascular injury from repetitive head impacts lead to a novel pattern on T2 FLAIR MRI? A hypothesis proposal and call for research.

The goal of this paper is to introduce the hypothesis that white matter (WM) and vascular injury are long-term consequences of repetitive head impacts (RHI) that result in a novel T2 fluid attenuated inversion recovery (FLAIR) magnetic resonance imaging pattern. A non-systematic literature review of autopsy and FLAIR studies of RHI-exposed adults was first conducted as a foundation for our hypothesis. A case series of RHI-exposed participants is presented to illustrate the unique FLAIR WM hyperintensities (WMH) pattern.

Characterizing white matter and vascular pathologies in brain donors exposed to repetitive head impacts.

Chronic traumatic encephalopathy (CTE) is a progressive brain disease linked to repetitive head impacts (RHI), often incurred from contact sports, and can lead to dementia. Here, we investigated the association between RHI and white matter/vascular neuropathologies and their relative contribution to dementia status in deceased men 50 + years old with and without exposure to RHI from various types of contact and collision sports. Our sample included two RHI groups from the UNITE brain bank: (1) American Football players (RHI-AF, n = 79), and (2) non-AF contact and collision sport athletes (e.

Prevention of concussion and long-term effects of repetitive traumatic brain injury: Unanimous consensus from the Cantu Concussion Summit.

Objective: The Cantu Concussion Summit aimed to gather clinicians and researchers to share findings and identify research gaps in brain injury and long-term cognitive disorders in athletes.

Design: The conference concluded with a discussion of ways to best mitigate the risk of concussion and repetitive traumatic brain injury (RTBI).

Setting And Participants: The summit was supported by an unrestricted educational grant from the National Football League and featured a diverse group of experts from multiple disciplines.

F-MK-6240 tau PET in patients at-risk for chronic traumatic encephalopathy.

Background: Molecular biomarkers of chronic traumatic encephalopathy (CTE) are lacking. We evaluated F-MK-6240 tau PET as a biomarker for CTE. Two studies were done: (1) H-MK-6240 autoradiography and an in-vitro brain homogenate binding studies on postmortem CTE tissue, (2) an in-vivo F-MK-6240 tau PET study in former American football players.

Perivascular glial reactivity is a feature of phosphorylated tau lesions in chronic traumatic encephalopathy.

Chronic traumatic encephalopathy (CTE), a neurodegenerative disease associated with repetitive head injuries, is characterised by perivascular hyperphosphorylated tau (p-tau) accumulations within the depths of cortical sulci. Although the majority of CTE literature focuses on p-tau pathology, other pathological features such as glial reactivity, vascular damage, and axonal damage are relatively unexplored. In this study, we aimed to characterise these other pathological features, specifically in CTE p-tau lesion areas, to better understand the microenvironment surrounding the lesion.

Loss of MEF2C function by enhancer mutation leads to neuronal mitochondria dysfunction and motor deficits in mice.

Background: Amyotrophic lateral sclerosis (ALS) is a fatal neurodegenerative disorder characterized by the loss of both upper and lower motor neurons, leading to progressive paralysis. Both genetic alterations and epigenetic modifications contribute to neuronal dysfunction in the pathogenesis of ALS. However, the mechanism behind genetic mutations in the non-coding region of genes that affect epigenetic modifications remains unclear.

Spatial proteomic differences in chronic traumatic encephalopathy, Alzheimer's disease, and primary age-related tauopathy hippocampi.

Introduction: Alzheimer's disease (AD), primary age-related tauopathy (PART), and chronic traumatic encephalopathy (CTE) all feature hyperphosphorylated tau (p-tau)-immunoreactive neurofibrillary degeneration, but differ in neuroanatomical distribution and progression of neurofibrillary degeneration and amyloid beta (Aβ) deposition.

Methods: We used Nanostring GeoMx Digital Spatial Profiling to compare the expression of 70 proteins in neurofibrillary tangle (NFT)-bearing and non-NFT-bearing neurons in hippocampal CA1, CA2, and CA4 subregions and entorhinal cortex of cases with autopsy-confirmed AD (n = 8), PART (n = 7), and CTE (n = 5).

Results: There were numerous subregion-specific differences related to Aβ processing, autophagy/proteostasis, inflammation, gliosis, oxidative stress, neuronal/synaptic integrity, and p-tau epitopes among these different disorders.

Associations Between Retinal Vascular Occlusions and Dementia.

Background/objectives: Retinal vascular occlusions, such as retinal vein occlusion (RVO) and retinal artery occlusion (RAO), are associated with cognitive impairment, including dementia. Our objective was to examine the odds of dementia among patients with retinal vascular occlusion.

Methods: This cross-sectional study included 474 patients with retinal vascular occlusion and 948 patients without retinal vascular occlusion (comparison group).

Neurodegeneration in the cortical sulcus is a feature of chronic traumatic encephalopathy and associated with repetitive head impacts.

Neurodegeneration is a seminal feature of many neurological disorders. Chronic traumatic encephalopathy (CTE) is caused by repetitive head impacts (RHI) and is characterized by sulcal tau pathology. However, quantitative assessments of regional neurodegeneration in CTE have not been described.

Duration of Ice Hockey Play and Chronic Traumatic Encephalopathy.

Importance: Chronic traumatic encephalopathy (CTE) is a neurodegenerative tauopathy associated with repetitive head impacts (RHIs). Prior research suggests a dose-response association between American football play duration and CTE risk and severity, but this association has not been studied for ice hockey.

Objective: To investigate associations of duration of ice hockey play with CTE diagnosis and severity, functional status, and dementia.

Transcriptome Signatures for Cognitive Resilience Among Individuals with Pathologically Confirmed Alzheimer Disease.

Introduction: Limited success to date in development of drugs that target hallmark Alzheimer disease (AD) proteins as a means to slow AD-related cognitive decline has sparked interest in approaches focused on cognitive resilience. We sought to identify transcriptome signatures among brain donors with neuropathologically confirmed AD that distinguish those with cognitive impairment from those that were cognitively intact.

Methods: We compared gene expression patterns in brain tissue from donors in four cohorts who were cognitively and pathologically normal (controls), met clinical and pathological criteria for AD (SymAD), or were cognitively normal prior to death despite pathological evidence of AD (cognitively resilient or AsymAD).

Lumipulse-Measured Cerebrospinal Fluid Biomarkers for the Early Detection of Alzheimer Disease.

Background And Objectives: CSF biomarkers of Aβ42 and phosphorylated tau (p-tau181) are used clinically for the detection of Alzheimer disease (AD) pathology during life. CSF biomarker validation studies have largely used clinical diagnoses and/or amyloid PET imaging as the reference standard. The few existing CSF-to-autopsy studies have been restricted to late-stage AD.

SHARD: an improved method for staining and visualizing multiplex immunofluorescence in optically cleared postmortem human brain tissue.

Postmortem human brain tissue is a critical resource for studying neurodegenerative disease, providing critical insights into cellular morphology, pathology, and network connectivity. To improve standard microscopy and enable high-resolution, three-dimensional (3D) images of tissues at the subcellular level, tissue-clearing methods have been developed. These 3D images allow for the analysis of large regions of interest and can be used to study structural and spatial changes that occur during neurodegeneration.