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Women who used estrogen-only hormone therapy later in life were less likely to develop dementia and showed fewer signs of Alzheimer’s disease in their brains, according to a large study of more than 21,000 participants. Hormone therapy use was linked to 39% lower odds of a dementia diagnosis and 35% lower odds of Alzheimer’s-related brain changes at autopsy, including amyloid plaques and tau tangles. Biomarker tests also suggested less amyloid buildup among hormone therapy users.

Mitochondria are essential metabolic and signalling hubs exposed to stress, and mitochondrial damage is highly detrimental to the cell. Mitophagy - the autophagy of mitochondria - is a key mechanism that maintains both mitochondrial integrity and metabolic flexibility. Mitophagy occurs via multiple pathways that either involve activation of PTEN-induced kinase 1 (PINK1) and the E3 ubiquitin-protein ligase Parkin, or are independent of PINK1 and Parkin. Recessive mutations in PINK1 and PKRN (the...

We developed a high-content screening to investigate how Alzheimer's disease (AD) genetic risk factors may affect synaptic mechanisms in rat primary neuronal cultures. Of the target genes identified, we found that Plcg2 downregulation in mouse dentate gyrus neurons consistently disrupted dendritic morphology and synaptic function. In human neuronal cultures (hNCs), PLCG2 downregulation also impaired synaptic function and increased amyloid-β (Aβ) levels and Tau phosphorylation. Very rare PLCG2...

Aging is the primary risk factor for chronic disease and is characterized by profound structural and architectural remodeling of human tissues. Here, we present a comprehensive assessment of these changes using 25,712 whole-slide histopathological images from 40 tissue types across 983 individuals in the Genotype-Tissue Expression cohort. By leveraging deep learning, we quantified nuanced morphological alterations to develop 'tissue clocks', predictors of biological age that reflect tissue...

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Understanding how brain connectivity reorganizes with age is essential for characterizing healthy aging. While static functional connectivity (sFC) has revealed broad age-related shifts in network segregation and integration, recent work underscores the need to examine how these patterns dynamically fluctuate over time to better understand cognitive decline and resilience in aging. The present resting-state fMRI study was conducted to enhance comprehension of the temporal variability and...

Hutchinson-Gilford Progeria Syndrome (HGPS) is a rare premature aging disorder caused by de novo LMNA mutations. Patients develop severe systemic symptoms limiting life quality and ultimately causing death from cardiovascular events. Despite extensive research, treatment options remain limited. Here, we investigated the role of long non-coding RNAs (lncRNAs) in the development of vascular pathology in HGPS. We analyzed an available single-cell RNA sequencing dataset from aortic arch cells of...

CONCLUSION: While the vast majority of the homebound population is frail or pre-frail, a considerable portion are not frail. Efforts to manage high-need, high-cost populations such as homebound older adults must account for the heterogeneity of the population with efforts to better understand the non-frail subpopulation and target interventions tailored to their needs with the goal of potentially reversing their homebound status.

Ovarian aging leads to infertility, endocrine dysregulation and increased chronic disease risk, yet there are currently no approved therapies to delay ovarian aging. Physical activity (PA) is a crucial lifestyle factor for human health and antiaging, but its effects and mechanisms on ovarian aging remain unclear. Here we show, through a cross-sectional analysis of 152,435 participants in the UK Biobank, that lower PA levels were observed among postmenopausal persons when compared to...

Aging is the primary risk factor for chronic disease and is characterized by profound structural and architectural remodeling of human tissues. Here, we present a comprehensive assessment of these changes using 25,712 whole-slide histopathological images from 40 tissue types across 983 individuals in the Genotype-Tissue Expression cohort. By leveraging deep learning, we quantified nuanced morphological alterations to develop 'tissue clocks', predictors of biological age that reflect tissue...

Spontaneous intracerebral hemorrhage (ICH) is a highly lethal and disabling form of stroke, in which hematoma expansion (HE) is a major and potentially modifiable determinant of early neurological deterioration and poor functional outcome. Computed tomography (CT) remains the first-line imaging modality for acute ICH and provides essential information for early HE risk stratification. However, current evidence is dispersed across conventional CT signs, composite scores, radiomics, machine...

Brain perivascular macrophages maintain brain physiology, yet their transcriptional regulators and functions in health and disease remain unclear. Using single-cell multi-omics and functional experiments, we identify cellular musculoaponeurotic fibrosarcoma oncogene (cMAF) as a key transcription factor for brain perivascular macrophages, and conditional deletion of cMAF disrupts their phenotype in vivo. Functionally, cMAF drives insulin-like growth factor-1 (IGF1) expression in perivascular...

CONCLUSIONS: Exercise improves balance, but modality choice should consider balance domain. Current estimates were most favourable for perturbation training in overall and static balance under supervision, sensory training at home, Tai Chi in global balance, Pilates in dynamic balance, and agility stepping or aquatic exercise in proactive balance. These estimates do not establish superiority. Dose should reflect task-specific challenge, safety and feasibility, because METs capture metabolic cost...

CONCLUSION: Moderate levels of green and blue spaces were associated with lower levels of biological aging. Nonlinear associations were stronger in socially vulnerable groups, suggesting that equitable nature-based planning could be a strategic public health intervention to promote healthy aging.

Graph theory provides unique tools to assess complex networks. It has been previously used with functional magnetic resonance imaging (fMRI) datasets to quantify macroscopic-scale connections among different brain regions, readily capturing brain network changes in subjects with Alzheimer's disease. Here, we apply graph theory to miniscope calcium imaging data recorded from the prefrontal cortex of freely behaving wild-type (WT) and Shank3^(fx) mice (a mouse model of autism) during social...

The choroid plexus (ChP) regulates cerebrospinal fluid homeostasis and immune surveillance, but its cellular organization and response to Alzheimer's disease (AD) remain incompletely defined. Here, we integrate single-nucleus RNA sequencing with spatial transcriptomics to generate a high-resolution atlas of the adult human ChP. We identify all major epithelial, stromal, and immune populations and resolve heterogeneity within macrophages, including a distinct subset expressing the giant protein...

Social interaction regulates neuronal excitability and behavior, and the lateral septum (LS) plays an important role in social behavior. However, the molecular mechanisms that support LS-dependent social responses remain unclear. Here, we show that neuronal activity-driven glucose transporter 4 (GLUT4) plasma translocation in LS GABAergic neurons supports social familiarity. Neuronal activation triggers CaMKIIα-mediated phosphorylation of GLUT4 at Ser243 and Ser254, which enhances Rab10 binding,...

The integrated stress response (ISR) enables cells to adapt to diverse cellular stresses, but during chronic or unresolved stress it becomes maladaptive and is implicated in neurodegenerative diseases, including Parkinson disease (PD). The mechanisms underlying maladaptive ISR-driven neurodegeneration, however, remain poorly defined. Here, we find a critical pathway by which chronic ISR activation promotes neurodegeneration in neurotoxin and α synucleinopathy models of PD in vitro and in vivo....

Gamma wave entrainment is a promising approach for improving cognitive function, particularly in the early stages of Alzheimer's disease. However, for everyday treatment, a light source system that maintains visibility while delivering effective stimulation is essential for patient comfort and practicality. To address this need, we developed organic light-emitting diode (OLED) glasses with optimized large-area transparent OLEDs for gamma wave entrainment. The optimization involved all layers of...

The choroid plexus (ChP) regulates cerebrospinal fluid homeostasis and immune surveillance, but its cellular organization and response to Alzheimer's disease (AD) remain incompletely defined. Here, we integrate single-nucleus RNA sequencing with spatial transcriptomics to generate a high-resolution atlas of the adult human ChP. We identify all major epithelial, stromal, and immune populations and resolve heterogeneity within macrophages, including a distinct subset expressing the giant protein...