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63 papers found.
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Neuropathological correlates and genetic architecture of microglial activation in elderly human brain

. Bennett 2 4 5 Philip L. De Jager 0 Center for Translational and Computational Neuroimmunology, Department of Neurology, Columbia University Medical Center , 630 West 168th Street, New York, NY 10032 , USA 1

Isoform-specific hyperactivation of calpain-2 occurs presymptomatically at the synapse in Alzheimer’s disease mice and correlates with memory deficits in human subjects

Calpain hyperactivation is implicated in late-stages of neurodegenerative diseases including Alzheimer’s disease (AD). However, calpains are also critical for synaptic function and plasticity, and hence memory formation and learning. Since synaptic deficits appear early in AD pathogenesis prior to appearance of overt disease symptoms, we examined if localized dysregulation of...

Polygenic analysis of inflammatory disease variants and effects on microglia in the aging brain

The role of the innate immune system in Alzheimer’s disease (AD) and neurodegenerative disease susceptibility has recently been highlighted in genetic studies. However, we do not know whether risk for inflammatory disease predisposes unaffected individuals to late-life cognitive deficits or AD-related neuropathology. We investigated whether genetic risk scores for seven immune...

Reproductive period and epigenetic modifications of the oxidative phosphorylation pathway in the human prefrontal cortex

participants for their participation to the studies and the staff of the Rush Alzhei Conceptualization: Riley M. Bove, Lori B. Chibnik. Data curation: Gyan Srivastava, Julie A. Schneider, David A. Bennett ... . Formal analysis: Ellis Patrick, Gyan Srivastava. Funding acquisition: Riley M. Bove, David A. Bennett, Philip L. De Jager. Investigation: Cristin McCabe Aubin, Gyan Srivastava. Resources: Philip L. De

Gene expression and DNA methylation are extensively coordinated with MRI-based brain microstructural characteristics

Cognitive function relies on both molecular levels and cellular structures. However, systematic relationships between these two components of cognitive function, and their joint contribution to disease, are largely unknown. We utilize postmortem neuroimaging in tandem with gene expression and DNA methylation, from 222 deeply-phenotyped persons in a longitudinal aging cohort...

Loneliness 5 years ante-mortem is associated with disease-related differential gene expression in postmortem dorsolateral prefrontal cortex

Subjective social isolation, loneliness, is associated with poor mental and physical health, but the underlying molecular mechanisms are poorly understood. Here we analyzed loneliness data collected on average 5 years ante-mortem and RNA gene expression at death in postmortem dorsolateral prefrontal cortex (DLPFC) from 181 participants in the Rush Memory and Aging Project (MAP...

Ex-vivo quantitative susceptibility mapping of human brain hemispheres

, Robert J. Dawe, Alifiya Kapasi, Julie A. Schneider. Formal analysis: Arnold M. Evia, Sue E. Leurgans, Konstantinos Arfanakis. Funding acquisition: David A. Bennett, Konstantinos Arfanakis

Genetic data and cognitively defined late-onset Alzheimer’s disease subgroups

Categorizing people with late-onset Alzheimer’s disease into biologically coherent subgroups is important for personalized medicine. We evaluated data from five studies (total n = 4050, of whom 2431 had genome-wide single-nucleotide polymorphism (SNP) data). We assigned people to cognitively defined subgroups on the basis of relative performance in memory, executive functioning...

Diurnal and seasonal molecular rhythms in human neocortex and their relation to Alzheimer’s disease

Jishu Xu in:Nature Research journals • PubMed • Google ScholarSearch for David A. Bennett in:Nature Research journals • PubMed • Google ScholarSearch for Philip L. De Jager in:Nature Research journals ... , Jishu Xu & Philip L. De JagerRush Alzheimer's Disease Center and Department of Neurological Sciences, Rush University Medical Center, 600 South Paulina Street, Chicago, Illinois 60612, USALei Yu & David A

APOE ε4-TOMM40 ‘523 haplotypes and the risk of Alzheimer’s disease in older Caucasian and African Americans

Patterns of linkage between the ε4 allele of Apolipoprotein E (APOE) and ‘523 poly-T alleles in the adjacent gene, TOMM40, differ between Caucasian and African Americans. The extent to which this difference affects the risk of Alzheimer’s disease (AD) is unclear. We compared the APOE ε4-TOMM40 ‘523 haplotypes between older Caucasian and African Americans, and examined their...

A translational approach to capture gait signatures of neurological disorders in mice and humans

A method for capturing gait signatures in neurological conditions that allows comparison of human gait with animal models would be of great value in translational research. However, the velocity dependence of gait parameters and differences between quadruped and biped gait have made this comparison challenging. Here we present an approach that accounts for changes in velocity...

A transcriptomic atlas of aged human microglia

With a rapidly aging global human population, finding a cure for late onset neurodegenerative diseases has become an urgent enterprise. However, these efforts are hindered by the lack of understanding of what constitutes the phenotype of aged human microglia—the cell type that has been strongly implicated by genetic studies in the pathogenesis of age-related neurodegenerative...

Decreased cortical FADD protein is associated with clinical dementia and cognitive decline in an elderly community sample

FADD (Fas-associated death domain) adaptor is a crucial protein involved in the induction of cell death but also mediates non-apoptotic actions via a phosphorylated form (p-Ser194-FADD). This study investigated the possible association of FADD forms with age-related neuropathologies, cognitive function, and the odds of dementia in an elderly community sample. FADD forms were...

Cognitive Decline Is Associated with Risk Aversion and Temporal Discounting in Older Adults without Dementia

Risk aversion and temporal discounting are preferences that are strongly linked to sub-optimal financial and health decision making ability. Prior studies have shown they differ by age and cognitive ability, but it remains unclear whether differences are due to age-related cognitive decline or lower cognitive abilities over the life span. We tested the hypothesis that cognitive...

Association of white matter hyperintensities and gray matter volume with cognition in older individuals without cognitive impairment

Both presence of white matter hyperintensities (WMH) and smaller total gray matter volume on brain magnetic resonance imaging (MRI) are common findings in old age, and contribute to impaired cognition. We tested whether total WMH volume and gray matter volume had independent associations with cognition in community-dwelling individuals without dementia or mild cognitive...

Plasma Exosomal miRNAs in Persons with and without Alzheimer Disease: Altered Expression and Prospects for Biomarkers

To assess the value of exosomal miRNAs as biomarkers for Alzheimer disease (AD), the expression of microRNAs was measured in a plasma fraction enriched in exosomes by differential centrifugation, using Illumina deep sequencing. Samples from 35 persons with a clinical diagnosis of AD dementia were compared to 35 age and sex matched controls. Although these samples contained less...

The Role of MAPT Haplotype H2 and Isoform 1N/4R in Parkinsonism of Older Adults

Background and Objective Recently, we have shown that the Parkinson’s disease (PD) susceptibility locus MAPT (microtubule associated protein tau) is associated with parkinsonism in older adults without a clinical diagnosis of PD. In this study, we investigated the relationship between parkinsonian signs and MAPT transcripts by assessing the effect of MAPT haplotypes on...

Temporal Discounting Is Associated with an Increased Risk of Mortality among Community-Based Older Persons without Dementia

Background Temporal discounting is an important determinant of many health and financial outcomes, but we are not aware of studies that have examined the association of temporal discounting with mortality. Methods Participants were 406 older persons without dementia from the Rush Memory and Aging Project, a longitudinal cohort study of aging. Temporal discounting was measured...