Background: The neuronal and gliaI populations within the brain are tightly interwoven, making isolation and study of large populations of a single cell type from brain tissue a major technical challenge. Concurrently, cell-type specific extracellular vesicles (EVs) hold enormous diagnostic and therapeutic potential in neurodegenerative disorders including Alzheimer's disease (AD).
New Method: Postmortem AD cortical samples were thawed and gently dissociated.
Objective: To examine participants' experiences with peer-support after lower limb loss (LLL) and the associations between the peer-support experience (perceived benefits and barriers) and mobility outcomes.
Design: Quantitative and qualitative descriptive study with a cross-sectional design.
Setting: National survey (distributed to 169 peer-support groups in 44 states in the US).
medRxiv
July 2023
Introduction: Vascular amyloid beta (Aβ) protein deposits were detected in retinas of mild cognitively impaired (MCI) and Alzheimer's disease (AD) patients. We tested the hypothesis that the retinal vascular tight junctions (TJs) were compromised and linked to disease status.
Methods: TJ components and Aβ expression in capillaries and larger blood vessels were determined in post mortem retinas from 34 MCI or AD patients and 27 cognitively normal controls and correlated with neuropathology.
Lang Speech Hear Serv Sch
July 2023
Purpose: This tutorial aims to introduce school-based speech-language pathologists (SLPs) to developmental systems theory as a framework for considering interactions across functional domains, such as language, vision, and motor, for students with complex needs.
Method: This tutorial summarizes the current literature on developmental systems theory in its application to working with students who have needs in multiple domains of functioning in addition to communication. A hypothetical case of a student, James, with cerebral palsy, cortical visual impairment, and complex communication needs, is presented to illustrate the primary tenets of the theory.
Alzheimer's disease (AD) pathologies were discovered in the accessible neurosensory retina. However, their exact nature and topographical distribution, particularly in the early stages of functional impairment, and how they relate to disease progression in the brain remain largely unknown. To better understand the pathological features of AD in the retina, we conducted an extensive histopathological and biochemical investigation of postmortem retina and brain tissues from 86 human donors.
View Article and Find Full Text PDFThe dentate gyrus (DG) is an integral portion of the hippocampal formation, and it is composed of three layers. Quantitative magnetic resonance (MR) imaging has the capability to map brain tissue microstructural properties which can be exploited to investigate neurodegeneration in Alzheimer's disease (AD). However, assessing subtle pathological changes within layers requires high resolution imaging and histological validation.
View Article and Find Full Text PDFBackground: Physical activity has been shown to be fundamental in the prevention of numerous diseases and disorders. Achieving and maintaining physical activity levels can be particularly challenging in those with impairments, such as those experiencing a lower limb amputation. To slow the spread of the virus, COVID-19 lockdown mandates imposed by the US state governments may have inadvertent consequences on physical activity levels of those dependent on specific forms of exercise.
View Article and Find Full Text PDFAbnormally phosphorylated tau, an indicator of Alzheimer's disease, accumulates in the first decades of life in the locus coeruleus (LC), the brain's main noradrenaline supply. However, technical challenges in in-vivo assessments have impeded research into the role of the LC in Alzheimer's disease. We studied participants with or known to be at-risk for mutations in genes causing autosomal-dominant Alzheimer's disease (ADAD) with early onset, providing a unique window into the pathogenesis of Alzheimer's largely disentangled from age-related factors.
View Article and Find Full Text PDFSynaptic transfer of tau has long been hypothesized from the human pathology pattern and has been demonstrated in vitro and in vivo, but the precise mechanisms remain unclear. Extracellular vesicles such as exosomes have been suggested as a mechanism, but not all tau is exosomal. The present experiments use a novel flow cytometry assay to quantify depolarization of synaptosomes by KCl after loading with FM2-10, which induces a fluorescence reduction associated with synaptic vesicle release; the degree of reduction in cryopreserved human samples equaled that seen in fresh mouse synaptosomes.
View Article and Find Full Text PDFIntracortical microelectrode arrays (MEA) can be used as part of a brain-machine interface system to provide sensory feedback control of an artificial limb to assist persons with tetraplegia. Variability in functionality of electrodes has been reported but few studies in humans have examined the impact of chronic brain tissue responses revealed postmortem on electrode performanceIn a tetraplegic man, recording MEAs were implanted into the anterior intraparietal area and Brodmann's area 5 (BA5) of the posterior parietal cortex and a recording and stimulation array was implanted in BA1 of the primary somatosensory cortex (S1). The participant expired from unrelated causes seven months after MEA implantation.
View Article and Find Full Text PDFBackground & Aims: Given that standardized language measures alone are inadequate for identifying functionally defined developmental language disorder (fDLD), this study investigated whether non-linguistic cognitive abilities (procedural learning, motor functions, executive attention, processing speed) can increase the prediction accuracy of fDLD in children in linguistically diverse settings.
Methods & Procedures: We examined non-linguistic cognitive abilities in mono- and bilingual school-aged children (ages 8-12) with and without fDLD. Typically developing (TD) children (14 monolinguals, 12 bilinguals) and children with fDLD (28 monolinguals, 12 bilinguals) completed tasks measuring motor functions, procedural learning, executive attention and processing speed.
There is a need to increase older adults' access and adherence to falls prevention strategies. This study aims to explore older adults' perceived barriers to participation in a fall prevention strategy. A qualitative descriptive approach was used.
View Article and Find Full Text PDFVerbal working memory (VWM) deficits are common in individuals with developmental language disorder (DLD) but are not well understood. This study evaluated how both memory and language production factors influence VWM performance in children and adults with DLD, focusing on the influence of serial position, phonological activation (PA), and lexical frequency. Participants were 30 children with DLD and 26 with typical language (TL), and 21 adults with DLD and 23 with TL.
View Article and Find Full Text PDFIn the current study, we evaluated behavioral and electrophysiological evidence to determine whether bilinguals differ from monolinguals in the efficiency of response inhibition. Bilinguals and matched monolingual controls performed the flanker task while behavioral and electrophysiological measures were collected. Participants were slower and less accurate in responding to incongruent trials, but the magnitude of the behavioral effect of congruence was not modulated by participant group.
View Article and Find Full Text PDFThe subiculum is the major output component of the hippocampal formation and one of the major brain structures most affected by Alzheimer's disease. Our previous work revealed a hidden laminar architecture within the mouse subiculum. However, the rotation of the hippocampal longitudinal axis across species makes it unclear how the laminar organization is represented in human subiculum.
View Article and Find Full Text PDFPurpose The aim of the current study was to investigate whether dual language experience modulates processing speed in typically developing (TD) children and in children with developmental language disorder (DLD). We also examined whether processing speed predicted vocabulary and sentence-level abilities in receptive and expressive modalities. Method We examined processing speed in monolingual and bilingual school-age children (ages 8-12 years) with and without DLD.
View Article and Find Full Text PDFPericyte loss and deficient vascular platelet-derived growth factor receptor-β (PDGFRβ) signaling are prominent features of the blood-brain barrier breakdown described in Alzheimer's disease (AD) that can predict cognitive decline yet have never been studied in the retina. Recent reports using noninvasive retinal amyloid imaging, optical coherence tomography angiography, and histological examinations support the existence of vascular-structural abnormalities and vascular amyloid β-protein (Aβ) deposits in retinas of AD patients. However, the cellular and molecular mechanisms of such retinal vascular pathology were not previously explored.
View Article and Find Full Text PDFPurpose The aim of the current study was to investigate whether dual language experience modulates the efficiency of the 3 attentional networks (alerting, orienting, and executive control) in typically developing (TD) children and in children with developmental language disorder (DLD). Method We examined the attentional networks in monolingual and bilingual school-aged children (ages 8-12 years) with and without DLD. TD children (35 monolinguals, 23 bilinguals) and children with DLD (17 monolinguals, 9 bilinguals) completed the Attention Network Test (Fan et al.
View Article and Find Full Text PDFNat Genet
September 2019
We present a new set of subjective Age of Acquisition (AoA) ratings for 299 words (158 nouns, 141 verbs) in seven languages from various language families and cultural settings: American English, Czech, Scottish Gaelic, Lebanese Arabic, Malaysian Malay, Persian, and Western Armenian. The ratings were collected from a total of 173 participants and were highly reliable in each language. We applied the same method of data collection as used in a previous study on 25 languages which allowed us to create a database of fully comparable AoA ratings of 299 words in 32 languages.
View Article and Find Full Text PDFApolipoprotein E (apoE) colocalizes with amyloid-β (Aβ) in Alzheimer disease (AD) plaques and in synapses, and evidence suggests that direct interactions between apoE and Aβ are important for apoE's effects in AD. The present work examines the hypothesis that apoE receptors mediate uptake of apoE/Aβ complex into synaptic terminals. Western blot analysis shows multiple SDS-stable assemblies in synaptosomes from human AD cortex; apoE/Aβ complex was markedly increased in AD compared with aged control samples.
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