Melissa J. Alldred
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View article: Aging, Rather than Genotype, Is the Principal Contributor to Differential Gene Expression Within Targeted Replacement APOE2, APOE3, and APOE4 Mouse Brain
Aging, Rather than Genotype, Is the Principal Contributor to Differential Gene Expression Within Targeted Replacement APOE2, APOE3, and APOE4 Mouse Brain Open
Background: Apolipoprotein E (APOE) is the strongest genetic risk determinant for late-onset Alzheimer’s disease (AD). The APOE3 allele is risk-neutral, the APOE4 allele increases the risk of developing AD, and the APOE2 allele is neuropro…
View article: Benefits of Maternal Choline Supplementation on Aged Basal Forebrain Cholinergic Neurons (BFCNs) in a Mouse Model of Down Syndrome and Alzheimer’s Disease
Benefits of Maternal Choline Supplementation on Aged Basal Forebrain Cholinergic Neurons (BFCNs) in a Mouse Model of Down Syndrome and Alzheimer’s Disease Open
Down syndrome (DS), stemming from the triplication of human chromosome 21, results in intellectual disability, with early mid-life onset of Alzheimer’s disease (AD) pathology. Early interventions to reduce cognitive impairments and neuropa…
View article: Frontal cortex pyramidal neuron expression profiles differentiate the prodromal stage from progressive degeneration across the Alzheimer's disease spectrum
Frontal cortex pyramidal neuron expression profiles differentiate the prodromal stage from progressive degeneration across the Alzheimer's disease spectrum Open
INTRODUCTION Underlying causes of Alzheimer's disease (AD) remain unknown, making it imperative to identify molecular mechanisms driving the pathobiology of AD onset and progression. METHODS Laser capture microdissection was used to isolat…
View article: Profiling lamina specific pyramidal neurons using postmortem human formalin fixed paraffin embedded frontal cortex tissue in combination with digital spatial profiling
Profiling lamina specific pyramidal neurons using postmortem human formalin fixed paraffin embedded frontal cortex tissue in combination with digital spatial profiling Open
This optimized DSP assay provides high resolution RNA-seq data demonstrating utility and versatility of the GeoMx platform for individually characterized neurons and isolated cortical ribbons within postmortem FFPE human brain tissue for d…
View article: Profiling hippocampal neuronal populations reveals unique gene expression mosaics reflective of connectivity-based degeneration in the Ts65Dn mouse model of Down syndrome and Alzheimer’s disease
Profiling hippocampal neuronal populations reveals unique gene expression mosaics reflective of connectivity-based degeneration in the Ts65Dn mouse model of Down syndrome and Alzheimer’s disease Open
Introduction Individuals with Down syndrome (DS) exhibit neurological deficits throughout life including the development of in Alzheimer’s disease (AD) pathology and cognitive impairment. At the cellular level, dysregulation in neuronal ge…
View article: Down syndrome frontal cortex layer III and layer V pyramidal neurons exhibit lamina specific degeneration in aged individuals
Down syndrome frontal cortex layer III and layer V pyramidal neurons exhibit lamina specific degeneration in aged individuals Open
View article: Analysis of microisolated frontal cortex excitatory layer III and V pyramidal neurons reveals a neurodegenerative phenotype in individuals with Down syndrome
Analysis of microisolated frontal cortex excitatory layer III and V pyramidal neurons reveals a neurodegenerative phenotype in individuals with Down syndrome Open
View article: Hippocampal CA1 Pyramidal Neurons Display Sublayer and Circuitry Dependent Degenerative Expression Profiles in Aged Female Down Syndrome Mice
Hippocampal CA1 Pyramidal Neurons Display Sublayer and Circuitry Dependent Degenerative Expression Profiles in Aged Female Down Syndrome Mice Open
Background: Individuals with Down syndrome (DS) have intellectual disability and develop Alzheimer’s disease (AD) pathology during midlife, particularly in the hippocampal component of the medial temporal lobe memory circuit. However, mole…
View article: Synthesis and Characterization of Click Chemical Probes for Single-Cell Resolution Detection of Epichaperomes in Neurodegenerative Disorders
Synthesis and Characterization of Click Chemical Probes for Single-Cell Resolution Detection of Epichaperomes in Neurodegenerative Disorders Open
Neurodegenerative disorders, including Alzheimer’s disease (AD) and Parkinson’s disease (PD), represent debilitating conditions with complex, poorly understood pathologies. Epichaperomes, pathologic protein assemblies nucleated on key chap…
View article: Apolipoprotein <scp>E2</scp> Expression Alters Endosomal Pathways in a Mouse Model With Increased Brain Exosome Levels During Aging
Apolipoprotein <span>E2</span> Expression Alters Endosomal Pathways in a Mouse Model With Increased Brain Exosome Levels During Aging Open
The polymorphic APOE gene is the greatest genetic determinant of sporadic Alzheimer's disease risk: the APOE4 allele increases risk, while the APOE2 allele is neuroprotective compared with the risk‐neutral APOE3 allele. The neuronal endoso…
View article: Early-life prefrontal cortex inhibition and early-life stress lead to long-lasting behavioral, transcriptional, and physiological impairments
Early-life prefrontal cortex inhibition and early-life stress lead to long-lasting behavioral, transcriptional, and physiological impairments Open
View article: Application of robust regression in translational neuroscience studies with non-Gaussian outcome data
Application of robust regression in translational neuroscience studies with non-Gaussian outcome data Open
Linear regression is one of the most used statistical techniques in neuroscience, including the study of the neuropathology of Alzheimer’s disease (AD) dementia. However, the practical utility of this approach is often limited because depe…
View article: Maternal choline supplementation protects against age-associated cholinergic and GABAergic basal forebrain neuron degeneration in the Ts65Dn mouse model of Down syndrome and Alzheimer's disease
Maternal choline supplementation protects against age-associated cholinergic and GABAergic basal forebrain neuron degeneration in the Ts65Dn mouse model of Down syndrome and Alzheimer's disease Open
Down syndrome (DS) is a genetic disorder caused by triplication of human chromosome 21. In addition to intellectual disability, DS is defined by a premature aging phenotype and Alzheimer's disease (AD) neuropathology, including septohippoc…
View article: Basal forebrain cholinergic neurons are vulnerable in a mouse model of Down syndrome and their molecular fingerprint is rescued by maternal choline supplementation
Basal forebrain cholinergic neurons are vulnerable in a mouse model of Down syndrome and their molecular fingerprint is rescued by maternal choline supplementation Open
Basal forebrain cholinergic neuron (BFCN) degeneration is a hallmark of Down syndrome (DS) and Alzheimer's disease (AD). Current therapeutics in these disorders have been unsuccessful in slowing disease progression, likely due to poorly un…
View article: Microisolation of Spatially Characterized Single Populations of Neurons for RNA Sequencing from Mouse and Postmortem Human Brain Tissues
Microisolation of Spatially Characterized Single Populations of Neurons for RNA Sequencing from Mouse and Postmortem Human Brain Tissues Open
Single-cell and single-population RNA sequencing (RNA-seq) is a rapidly evolving new field of intense investigation. Recent studies indicate unique transcriptomic profiles are derived based on the spatial localization of neurons within cir…
View article: Correction to: Profiling Basal Forebrain Cholinergic Neurons Reveals a Molecular Basis for Vulnerability Within the Ts65Dn Model of Down Syndrome and Alzheimer’s Disease
Correction to: Profiling Basal Forebrain Cholinergic Neurons Reveals a Molecular Basis for Vulnerability Within the Ts65Dn Model of Down Syndrome and Alzheimer’s Disease Open
View article: Aging in Down Syndrome: Latest Clinical Advances and Prospects
Aging in Down Syndrome: Latest Clinical Advances and Prospects Open
Down syndrome (DS), or trisomy 21, is the most common genetic cause of intellectual disability [...]
View article: Aging with Down Syndrome—Where Are We Now and Where Are We Going?
Aging with Down Syndrome—Where Are We Now and Where Are We Going? Open
Down syndrome (DS) is a form of accelerated aging, and people with DS are highly prone to aging-related conditions that include vascular and neurological disorders. Due to the overexpression of several genes on Chromosome 21, for example g…
View article: Oxidative Phosphorylation Is Dysregulated Within the Basocortical Circuit in a 6-month old Mouse Model of Down Syndrome and Alzheimer’s Disease
Oxidative Phosphorylation Is Dysregulated Within the Basocortical Circuit in a 6-month old Mouse Model of Down Syndrome and Alzheimer’s Disease Open
Down syndrome (DS) is the primary genetic cause of intellectual disability (ID), which is due to the triplication of human chromosome 21 (HSA21). In addition to ID, HSA21 trisomy results in a number of neurological and physiological pathol…
View article: Profiling Basal Forebrain Cholinergic Neurons Reveals a Molecular Basis for Vulnerability Within the Ts65Dn Model of Down Syndrome and Alzheimer’s Disease
Profiling Basal Forebrain Cholinergic Neurons Reveals a Molecular Basis for Vulnerability Within the Ts65Dn Model of Down Syndrome and Alzheimer’s Disease Open
View article: Adiponectin Modulation by Genotype and Maternal Choline Supplementation in a Mouse Model of Down Syndrome and Alzheimer’s Disease
Adiponectin Modulation by Genotype and Maternal Choline Supplementation in a Mouse Model of Down Syndrome and Alzheimer’s Disease Open
Down syndrome (DS) is a genetic disorder caused by the triplication of human chromosome 21, which results in neurological and physiological pathologies. These deficits increase during aging and are exacerbated by cognitive decline and incr…
View article: Mitovesicles are a novel population of extracellular vesicles of mitochondrial origin altered in Down syndrome
Mitovesicles are a novel population of extracellular vesicles of mitochondrial origin altered in Down syndrome Open
Newly identified mitovesicles are a type of extracellular vesicles whose levels and cargo are altered in Down syndrome.
View article: Profiling Basal Forebrain Cholinergic Neurons Reveals a Molecular Basis for Vulnerability Within the Ts65Dn&nbsp;Model of Down Syndrome and Alzheimer’s Disease
Profiling Basal Forebrain Cholinergic Neurons Reveals a Molecular Basis for Vulnerability Within the Ts65Dn Model of Down Syndrome and Alzheimer’s Disease Open
Background: Basal forebrain cholinergic neuron (BFCN) degeneration is a hallmark of Down syndrome (DS) and Alzheimer’s disease (AD). Current therapeutics have been unsuccessful in slowing disease progression, likely due to complex patholog…
View article: Long‐term effects of maternal choline supplementation on CA1 pyramidal neuron gene expression in the Ts65Dn mouse model of Down syndrome and Alzheimer's disease
Long‐term effects of maternal choline supplementation on CA1 pyramidal neuron gene expression in the Ts65Dn mouse model of Down syndrome and Alzheimer's disease Open
Choline is critical for normative function of 3 major pathways in the brain, including acetylcholine biosynthesis, being a key mediator of epigenetic regulation, and serving as the primary substrate for the phosphatidylethanolamine N ‐meth…
View article: Maternal Choline Supplementation Alters Basal Forebrain Cholinergic Neuron Gene Expression in the Ts65Dn Mouse Model of Down Syndrome
Maternal Choline Supplementation Alters Basal Forebrain Cholinergic Neuron Gene Expression in the Ts65Dn Mouse Model of Down Syndrome Open
Down syndrome (DS), trisomy 21, is marked by intellectual disability and a premature aging profile including degeneration of the basal forebrain cholinergic neuron (BFCN) projection system, similar to Alzheimer's disease (AD). Although dat…
View article: Apolipoprotein E4 genotype compromises brain exosome production
Apolipoprotein E4 genotype compromises brain exosome production Open
In addition to being the greatest genetic risk factor for Alzheimer's disease, expression of the ɛ4 allele of apolipoprotein E can lead to cognitive decline during ageing that is independent of Alzheimer's amyloid-β and tau pathology. In h…
View article: CA1 pyramidal neuron gene expression mosaics in the Ts65Dn murine model of Down syndrome and Alzheimer's disease following maternal choline supplementation
CA1 pyramidal neuron gene expression mosaics in the Ts65Dn murine model of Down syndrome and Alzheimer's disease following maternal choline supplementation Open
Although there are changes in gene expression and alterations in neuronal density and afferent inputs in the forebrain of trisomic mouse models of Down syndrome (DS) and Alzheimer's disease (AD), there is a lack of systematic assessments o…
View article: Expression profiling suggests microglial impairment in human immunodeficiency virus neuropathogenesis
Expression profiling suggests microglial impairment in human immunodeficiency virus neuropathogenesis Open
Objective CD16 + /CD163 + macrophages (MΦs) and microglia accumulate in the brains of patients with human immunodeficiency virus (HIV) encephalitis (HIVE), a neuropathological correlate of the most severe form of HIV‐associated neurocognit…
View article: Enhanced exosome secretion in Down syndrome brain - a protective mechanism to alleviate neuronal endosomal abnormalities
Enhanced exosome secretion in Down syndrome brain - a protective mechanism to alleviate neuronal endosomal abnormalities Open
A dysfunctional endosomal pathway and abnormally enlarged early endosomes in neurons are an early characteristic of Down syndrome (DS) and Alzheimer's disease (AD). We have hypothesized that endosomal material can be released by endosomal …
View article: Autophagy flux in CA1 neurons of Alzheimer hippocampus: Increased induction overburdens failing lysosomes to propel neuritic dystrophy
Autophagy flux in CA1 neurons of Alzheimer hippocampus: Increased induction overburdens failing lysosomes to propel neuritic dystrophy Open
Defective autophagy contributes to Alzheimer disease (AD) pathogenesis although evidence is conflicting on whether multiple stages are impaired. Here, for the first time, we have comprehensively evaluated the entire autophagic process spec…