Early-Life Parental Affection, Social Relationships in Adulthood, and Later-Life Cognitive Function.

Objective: Although research has demonstrated the long-term health consequences of childhood adversities, less is known about the long-term impact of positive childhood experiences, such as parental affection.

Method: Using longitudinal data (1995-2014) from the Midlife in the United States (MIDUS) study, we analyze structural equation models estimating direct and indirect pathways from early-life parental affection to changes in later-life cognitive function through relationship quality in adulthood among Black and White older adults ( = 1983).

Results: Analyses revealed significant indirect effects of parental affection on better cognitive function through higher levels of social support (both average social support and family social support) in adulthood in the full sample and among Black respondents.

SMOC1 colocalizes with Alzheimer's disease neuropathology and delays Aβ aggregation.

SMOC1 has emerged as one of the most significant and consistent new biomarkers of early Alzheimer's disease (AD). Recent studies show that SMOC1 is one of the earliest changing proteins in AD, with levels in the cerebrospinal fluid increasing many years before symptom onset. Despite this clear association with disease, little is known about the role of SMOC1 in AD or its function in the brain.

Pathologic and clinical correlates of region-specific brain GFAP in Alzheimer's disease.

Plasma glial fibrillary acidic protein (GFAP) is an emerging biomarker of Alzheimer's disease (AD), with higher blood GFAP levels linked to faster cognitive decline, particularly among individuals with high brain amyloid burden. However, few studies have examined brain GFAP expression to clarify if peripheral associations reflect brain changes. This study aimed to correlate region-specific GFAP mRNA expression (n = 917) and protein abundance (n=386) with diverse neuropathological measures at autopsy in the Religious Orders Study and Rush Memory and Aging Project (ROS/MAP) and to characterize the interaction between brain GFAP and brain amyloid burden on downstream outcomes.

Improved Function After Anterior Controllable Antedisplacement and Fusion for Cervical Ossification of Posterior Longitudinal Ligament: A Long-Term Follow-Up.

Background: Anterior controllable antedisplacement and fusion (ACAF) is an emerging surgical approach for treating cervical ossification of the posterior longitudinal ligament (C-OPLL), yet there is limited data on its long-term efficacy and safety. The present study aimed to analyze the short- and long-term postoperative clinical and radiological outcomes and perioperative complications of ACAF for patients with C-OPLL.

Methods: This was a single-center, retrospective, cohort study, with the mean duration of follow-up of at least 24 months.

Biological validation of peak-width of skeletonized mean diffusivity as a VCID biomarker: The MarkVCID Consortium.

Background: Peak-width of skeletonized mean diffusivity (PSMD), a neuroimaging marker of cerebral small vessel disease (SVD), has shown excellent instrumental properties. Here, we extend our work to perform a biological validation of PSMD.

Methods: We included 396 participants from the Biomarkers for Vascular Contributions to Cognitive Impairment and Dementia (MarkVCID-1) Consortium and three replication samples (Cohorts for Heart and Aging Research in Genomic Epidemiology = 6172, Rush University Medical Center = 287, University of California Davis Alzheimer's Disease Research Center = 567).

Temporal Sequence of Incident Mild Cognitive Impairment, Incident Parkinsonism, and Risk of Death in Unimpaired Community-Dwelling Older Adults.

Background: Mild cognitive impairment (MCI) and parkinsonism affect many older adults. The objective of this study was to determine the sequence of their occurrence and associated risk of death.

Methods: A total of 1255 community-dwelling unimpaired participants from 2 epidemiological cohorts were examined annually.

Large-scale deep proteomic analysis in Alzheimer's disease brain regions across race and ethnicity.

Introduction: Alzheimer's disease (AD) is the most prevalent neurodegenerative disease, yet our comprehension predominantly relies on studies within non-Hispanic White (NHW) populations. Here we provide an extensive survey of the proteomic landscape of AD across diverse racial/ethnic groups.

Methods: Two cortical regions, from multiple centers, were harmonized by uniform neuropathological diagnosis.

Epistatic effects of IGHG and FCGRIIB genes on the development of Alzheimer's disease in African Americans.

Genome-wide association studies (GWAS) of Alzheimer's disease (AD) have identified a large number of susceptibility genes, but most of AD heritability remains unexplained, implying the existence of additional genes. Furthermore, the majority of the GWAS have been conducted in people of European descent, and the genes important for AD susceptibility in people of African descent have been underexplored. In this hypothesis-generating prospective cohort study, we genotyped 191 African Americans (AAs) from three longitudinal cohorts on aging for the IgG3 allotype GM6, which is expressed exclusively in people of African descent, and assessed its interaction with IGHG, FCGRIIB, and HLA-DRB1 genes.

Integration across biophysical scales identifies molecular and cellular correlates of person-to-person variability in human brain connectivity.

Brain connectivity arises from interactions across biophysical scales, ranging from molecular to cellular to anatomical to network level. To date, there has been little progress toward integrated analysis across these scales. To bridge this gap, from a unique cohort of 98 individuals, we collected antemortem neuroimaging and genetic data, as well as postmortem dendritic spine morphometric, proteomic and gene expression data from the superior frontal and inferior temporal gyri.

Effects of brain microRNAs in cognitive trajectory and Alzheimer's disease.

microRNAs (miRNAs) have a broad influence on gene expression; however, we have limited insights into their contribution to rate of cognitive decline over time or Alzheimer's disease (AD). Given this, we tested associations of 528 miRNAs with cognitive trajectory, AD hallmark pathologies, and AD clinical diagnosis using small RNA sequencing from the dorsolateral prefrontal cortex of 641 community-based donors. We found 311 miRNAs differentially expressed in AD or its endophenotypes after adjusting for technical and sociodemographic variables.

An analysis of RNA quality metrics in human brain tissue.

Human brain tissue studies have historically used a range of metrics to assess RNA quality. However, few large-scale cross-comparisons of pre-sequencing quality metrics with RNA-seq quality have been published. Here, we analyze how well metrics gathered before RNA sequencing (post-mortem interval (PMI) and RNA integrity number RIN) relate to analyses of RNA quality after sequencing (Percent of counts in Top Ten genes (PTT), 5' bias, and 3' bias) as well as with individual gene counts across the transcriptome.

Association of MIND diet with cognitive decline among Black and White older adults.

Introduction: We examined the Mediterranean-Dietary Approaches to Stop Hypertension Intervention for Neurodegenerative Delay (MIND) diet's association with cognitive decline by race among older adults in the Chicago Health and Aging Project.

Methods: Five thousand two hundred fifty-nine participants (73.5 [± 6.

A cross-disease resource of living human microglia identifies disease-enriched subsets and tool compounds recapitulating microglial states.

Human microglia play a pivotal role in neurological diseases, but we still have an incomplete understanding of microglial heterogeneity, which limits the development of targeted therapies directly modulating their state or function. Here, we use single-cell RNA sequencing to profile 215,680 live human microglia from 74 donors across diverse neurological diseases and CNS regions. We observe a central divide between oxidative and heterocyclic metabolism and identify microglial subsets associated with antigen presentation, motility and proliferation.