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Temporary ruling brings relief, but could be followed by a new wave of firings

A promising therapeutic intervention for preventing the onset and progression of Alzheimer's Disease (AD) is to protect and improve synaptic resilience, a well-established early vulnerability associated with the toxic effects of oligomers of Aβ (AβO) and Tau (TauO). We have previously reported that exosomes from hippocampal neural stem cells (NSCs) protect synapses against AβO. Here, we demonstrate how exosomes can also shield against TauO toxicity in adult mice synapses, potentially benefiting...

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A rare variant of Apolipoprotein E3 with neuroprotective properties has been identified in autosomal-dominant Alzheimer's disease. In this issue of Neuron, Chen et al.¹ show that direct interaction between this variant and tau blocks tau pathogenesis in rodent models.

Alzheimer's disease (AD) therapies utilizing amyloid-β (Aβ) immunization have shown potential in clinical trials. Yet, the mechanisms driving Aβ clearance in the immunized AD brain remain unclear. Here, we use spatial transcriptomics to explore the effects of both active and passive Aβ immunization in the AD brain. We compare actively immunized patients with AD with nonimmunized patients with AD and neurologically healthy controls, identifying distinct microglial states associated with Aβ...

CONCLUSION: Apigenin upregulates EIF6 expression and mitigates H2O2-induced chondrocyte senescence, highlighting its potential as a therapeutic agent for KOA. These findings provide insights into the nutritional health benefits of Apigenin and its implications for KOA treatment.

The aging of hematopoietic stem cells (HSCs) substantially alters their characteristics. Mitochondria, essential for cellular metabolism, play a crucial role, and their dysfunction is a hallmark of aging-induced changes. The impact of mitochondrial mass on aged HSCs remains incompletely understood. Here we demonstrate that HSCs with high mitochondrial mass during aging are not merely cells that have accumulated damaged mitochondria and become exhausted. In addition, these HSCs retain a high...

Epigenetic aging clocks represent contemporary aging biomarkers that predict age using methylomic data. These models can be categorized as first-generation clocks that estimate chronological age or next-generation clocks that are designed to associate with health, lifestyle, and/or outcomes. Recently, we created a next-generation buccal clock called CheekAge that associates with all-cause mortality risk in older adults. To better understand our model, we collated 25 Infinium MethylationEPIC...

Biological age is an important measure of aging that reflects an individual's physical health and is linked to various diseases. Current prediction models are still limited in precision, and the risk factors for accelerated aging remain underexplored. Therefore, we aimed to develop a precise biological age and assess the impact of socio-demographic and behavioral patterns on the aging process.We utilized Deep Neural Networks (DNN) to construct biological age from participants with physical...

Ageing is associated with a range of chronic diseases and has diverse hallmarks. Mitochondrial dysfunction is implicated in ageing, and mouse-models with artificially enhanced mitochondrial DNA mutation rates show accelerated ageing. A scarcely studied aspect of ageing, because it is invisible in aggregate analyses, is the accumulation of somatic mitochondrial DNA mutations which are unique to single cells (cryptic mutations). We find evidence of cryptic mitochondrial DNA mutations from diverse...

CONCLUSION: This study provided real-world empirical cost estimates of AD burden in Malaysia. Informal care is a significant contributor to the societal cost of AD. Optimal healthcare resource allocation is essential in the decision making of healthcare stakeholders to address rising demands.

The maturation and stabilization of appropriate synaptic connections is a vital step in neural circuit development; however, the molecular signals underlying these processes are not fully understood. We show that astrocytes, through production of glypican 5 (GPC5), are required for maturation and refinement of synapses in the mouse cortex during the critical period. In the absence of astrocyte GPC5, thalamocortical synapses show structural immaturity, including smaller presynaptic terminals,...

Nicotinamide adenine dinucleotide kinase (NADK) is essential to the generation of nicotinamide adenine dinucleotide phosphate (NADP(H)), an important metabolic coupling factor involved in glucose-stimulated insulin secretion. In the present study, we showed that the expression of Nadk and Nadk2 transcripts and NADP(H) content were lower in islets of 80-week-old (aged) mice than those of 8-week-old (young) mice. This was associated with diminished oral glucose tolerance of old mice and the...

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