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CONCLUSIONS: Using cross-population GWAS meta-analyses, we identify novel LOAD susceptibility loci in/near LRRC4C and LHX5-AS1, both with known roles in neuronal development, as well as several novel population-unique loci. Reflecting the power of diverse ancestry in GWAS, we detect the SHARPIN locus with only 13.7% of the sample size of the NHW GWAS study (n = 409,589) in which this locus was first observed. Continued expansion into larger multi-ancestry studies will provide even more power for...

Using multi-echo blood oxygenation level-dependent (BOLD) neuroimaging, we examined lifespan differences in three subcortical nuclei important to the neuromodulation of cognition and target sites for early Alzheimer's pathogenesis in the isodendritic core: the locus coeruleus (LC) the major source of noradrenaline, the nucleus basalis of Meynert (NBM) the major source of acetylcholine, and the ventral tegmental area (VTA) the major source of dopamine. Seventy-one participants, from 19 to 86...

CONCLUSIONS AND IMPLICATIONS: Within this prospective cohort analysis, low CC emerged as a new independent risk factor for incident sarcopenia over 3 years, with a concomitant escalation in risk observed with severe diminution of CC.

The intensive production and use of plastics, poor biodegradability and inadequate recycling have caused excessive and alarming environmental pollution. This has led to the inevitable intake by humans, through different routes, of small plastic particles, the micro and nano-plastics (MNPs) with sizes ranging from nanometers (<1000 nm) to micrometers (from 5 mm to 1 µm). MNPs can cause harmful effects in human tissues and organs, contributing to the early onset of aging and various age-related...

Given the growing global elderly population and the accelerating decrease in grey matter volume (GMV) with age, understanding healthy brain aging is increasingly important. This study investigates whether variations in modifiable traits can account for differences in GMV and whether these traits can inform strategies to mitigate risks of future brain disorders. We identified 66 traits significantly associated with total GMV. Further, we examined the joint contributions of different domain traits...

Ageing is a prevalent characteristic of all cells, tissues, and organs; certain ones, such as the ovaries, undergo significant ageing and do so early in the lifespan of mammals. Despite the widely recognized hormonal regulation occurring in the ovaries, numerous mechanisms influencing ovarian ageing remain unclear. Recently, a long-overlooked consequence of splicing, small RNA molecules, characterized by their circular structure, have gained attention. Circular RNAs (circRNAs) have been...

BIN1, a late-onset Alzheimer's disease (LOAD) risk gene, is an endocytic regulator with an unclear synaptic function. We find Bin1 more prominently in inhibitory synapses (vGAT positive) than in excitatory ones (vGLUT1 positive). Bin1 knockdown reduces inhibitory synapses independently of Aβ42 production, increasing GABA release from the remaining synapses due to accelerated vGAT exocytosis and endocytosis, which decreases the size of inhibitory synaptic endosomes. In excitatory synapses, Bin1...

The misclassification of functional genomic loci as pseudogenes has long obscured critical regulators of cellular homeostasis, particularly in aging-related pathways. One such locus, originally annotated as RPL29P31, encodes a 17-kDa protein now redefined as PERMIT (Protein that Mediates ER-Mitochondria Trafficking). Through rigorous experimental validation-including antibody development, gene editing, lipidomics, and translational models-p17/PERMIT has emerged as a previously unrecognized...

CONCLUSION: GS research is transitioning from fundamental mechanisms to clinical diagnostics and therapeutics. Future advancements necessitate the integration of multimodal imaging technologies and interdisciplinary collaboration to facilitate early AD diagnosis and therapeutic target development. This study represents the first systematic construction of a knowledge framework for this field, providing theoretical foundations for optimizing research strategies and translational pathways.

INTRODUCTION: The entorhinal cortex (EC)-hippocampus system is critical for memory and affected early in Alzheimer's disease (AD). Cognitive dysfunction in AD is linked to neuropathological changes, including non-heme iron accumulation in vulnerable brain regions. This study characterized iron distribution in the EC-hippocampus system using ultra-high field (UHF) magnetic resonance imaging (MRI) at 7 Tesla (T) in aging and mild cognitive impairment (MCI), an AD at-risk state.

The increasing prevalence of neurodegenerative diseases in an aging population underscores the critical need for reliable biomarkers distinguishing normal aging from pathological neurodegeneration. This study leverages neuroimaging to identify age-resilient biomarkers, establishing a baseline of neural features that are relatively stable across the aging process. Our research objectives are threefold: (a) Validate a methodology using leverage scores to identify age-robust neural signatures; (b)...

CONCLUSION: Increased arterial stiffness and reduced CBF were not independently associated with smaller HV. However, in combination, persistently elevated AS and reduced CBF is associated with smaller HV. These effects were equally exerted across all hippocampal subfields tested. Our findings suggest a lag effect in the arterial stiffness and hippocampal volume relationship. We propose that the subsequent reduction in cerebral blood flow observed with elevated arterial stiffness may be the...

Science, Volume 389, Issue 6757, July 2025.

Science, Volume 389, Issue 6757, July 2025.