National Institute on Aging

iPSC neurodegenerative disease initiative isogenic CAG repeat iPSC line for Huntington's disease

Purpose of Research: in the KOLF2.1J background as an additional disease series within the iPSC Neurodegenerative Disease Initiative (iNDI) collection. Major Findings: KO, were capable of differentiating to striatal and cortical neurons, astrocytes and microglia using established...

Exploring transcriptomic and genomic latent variable correction approaches in differential expression analysis

Abstract Background Differential expression analysis is a central tool for studying the biological processes altered in human diseases via transcriptomic signatures. However, transcriptomic datasets are systematically confounded by latent variables from two distinct sources: unme...

Neurodegenerative disease risk associated with gene expression in peripheral monocytes across ancestries

Abstract It is hypothesised that peripheral immune states responding to regional environmental triggers contribute to central neurodegeneration. Region-specific genetic selection pressures require this hypothesis to be assessed in an ancestry-specific manner. Here, we utilise gen...

Cerebellar α-synucleinopathy contributes to Parkinsonian gait and balance impairment in mouse models

Postural instability and gait difficulty (PIGD) represent a debilitating clinical subtype of Parkinson’s disease (PD) that is largely refractory to dopaminergic replacement therapy. While clinical imaging implies that the cerebellum is involved in these axial deficits, the specif...

Blood proteomics of menopause map to brain aging and dementia risk

Abstract Menopause is a hallmark process in biological aging that has been implicated in later neurodegenerative risk, but the pathways underlying this connection remain unclear. Here we used blood proteomics data from several cohorts to identify biological changes associated wit...

Sex-specific biological aging clocks across organs and omics

Sex differentially shapes aging, neurodevelopment and neurodegenerative diseases such as Alzheimer’s disease (AD). However, most biological aging clocks (artificial intelligence-predicted age minus chronological age) were trained on sex-pooled samples and implicitly assume sex in...

Late-life semaglutide treatment slows ageing and extends lifespan in female mice

Abstract Pharmacological glucagon-like peptide-1 receptor (GLP-1R) activation reduces food intake and is an effective therapy for type 2 diabetes and obesity 1 . The use of GLP-1 medicines has revealed pleiotropic beneficial effects beyond glucose and weight control 2–5 , but lit...

Robust inference and correlates from genetic associations with personality

Personality traits describe stable differences in how people think, feel and behave, and how they interact with and experience their social and physical environments1,2. Many questions remain unanswered about associations between DNA and personality traits, such as their robustne...

The interplay of air pollution with plasma neurodegenerative markers and metabolome for dementia, Parkinson’s disease and all-cause mortality risks and transitions: The UK Biobank study

We investigated the joint associations of circulating neurodegeneration markers—neurofilament light (NfL) and glial fibrillary acidic protein (GFAP)—ambient air pollution, and plasma metabolomic profiles with transitions from a healthy state to dementia, Parkinson’s disease (PD),...

Association Between Changes in Perceived Neighborhood and Cognitive Performance Within Healthy Aging in Neighborhoods of Diversity Across the Life Span (HANDLS) Black Adults

Perceived neighborhood characteristics are related to cognitive performance. However, limited studies have examined how changes in neighborhood characteristics relate to cognitive performance, particularly among Black adults who are likely to experience changes in their residenti...

Endothelial Cell Proteins as Biomarkers in Susac Syndrome

ABSTRACT Objective Susac syndrome (SS) is a rare CD8 + T cell–mediated microangiopathy affecting the brain, retina, and auditory labyrinth. Endothelial injury is thought to be a central mechanism; however, no circulating disease biomarkers are known. We performed targeted proteom...

Association between self-reported oral health issues and autoimmune diseases: evidence from UK biobank

Oral microbiome dysbiosis may contribute to autoimmune disease development, but epidemiological evidence linking oral health and autoimmune disease risk is limited. To evaluate the association between self-reported oral health issues by questionnaire—defined as the presence of pa...