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Insights into the toxic effects of micro-nano-plastics on the human brain and their relationship with the onset of neurological diseases: A narrative review

1 month ago
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...
Carmela Rita Balistreri

AI-guided patient stratification improves outcomes and efficiency in the AMARANTH Alzheimer's Disease clinical trial

1 month ago
Alzheimer's Disease (AD) drug discovery has been hampered by patient heterogeneity, and the lack of sensitive tools for precise stratification. Here, we demonstrate that our robust and interpretable AI-guided tool (predictive prognostic model, PPM) enhances precision in patient stratification, improving outcomes and decreasing sample size for a AD clinical trial. The AMARANTH trial of lanabecestat, a BACE1 inhibitor, was deemed futile, as treatment did not change cognitive outcomes, despite...
Delshad Vaghari

Amyloid-β disrupts APP-regulated protein aggregation and dissociation from recycling endosomal membranes

1 month ago
Secretory proteins aggregate into non-soluble dense-core granules in recycling endosome-like compartments prior to regulated release. By contrast, aberrantly processed, secreted amyloid-β (Aβ) peptides derived from amyloid precursor protein (APP) form pathological extracellular amyloidogenic aggregations in late-stage Alzheimer's disease (AD). By examining living Drosophila prostate-like secondary cells, we show that both APP and Aβ peptides affect normal biogenesis of dense-core granules. These...
Preman J Singh

Multi-ancestry genome-wide meta-analysis of 56,241 individuals identifies known and novel cross-population and ancestry-specific associations as novel risk loci for Alzheimer's disease

1 month ago
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...
Farid Rajabli

Blood oxygenation level-dependent responses in neuromodulatory nuclei and their associations with attention and memory across age groups

1 month ago
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...
Elizabeth Riley

Insights into the toxic effects of micro-nano-plastics on the human brain and their relationship with the onset of neurological diseases: A narrative review

1 month ago
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...
Carmela Rita Balistreri

Modifiable traits and genetic associations with grey matter volume in mid-to-late adulthood: a population-based study in the UK biobank

1 month ago
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...
Guoqing Pan

Circular RNAs as regulators and biomarkers of mammalian ovarian ageing

1 month ago
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...
Arkadiusz Grzeczka

Alzheimer's genetic risk factor Bin1 controls synapse vesicle exo-endocytosis in inhibitory synapses

1 month ago
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...
Mariana A Barata

Beyond the Pseudogene: p17/PERMIT as a Mitochondrial Trafficking Protein Linking Aging and Neurodegeneration

1 month ago
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...
Onder Albayram

Research hotspots and frontiers of glymphatic system and Alzheimer's disease: a bibliometrics analysis

1 month ago
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.
Shichao Liu