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The R136S mutation in the APOE3 gene confers resilience against tau pathology via inhibition of the cGAS-STING-IFN pathway

7 months 1 week ago
The Christchurch mutation (R136S) in the APOE3 (E3S/S) gene is associated with attenuated tau load and cognitive decline despite the presence of a causal PSEN1 mutation and high amyloid burden in the carrier. However, the molecular mechanisms enabling the E3S/S mutation to mitigate tau-induced neurodegeneration remain unclear. Here, we replaced mouse Apoe with wild-type human APOE3 or APOE3S/S on a tauopathy background. The R136S mutation decreased tau load and protected against tau-induced...
Sarah Naguib

Granzyme K<sup>+</sup> CD8 T cells slow tauopathy progression by targeting microglia

7 months 1 week ago
Neurodegenerative diseases activate innate and adaptive immune responses that can either slow or accelerate disease progression. Here, we sought to define beneficial immune pressures that emerge during tauopathy development in mice and humans. Using mice that express mutant human tau in neurons, we observed that microglia slowed tauopathy development by controlling the spread of phosphorylated tau (pTau) in the central nervous system and blood. However, over time microglia converted into...
Hannah D Mason

Indicators of mortality risk in ageing horses

7 months 1 week ago
Clinical care for patients with limited life expectancy often requires adjustments, prioritizing immediate benefits over long-term outcomes, as the relevance of future complications diminishes. This study identifies indicators of mortality risk in horses with chronic orthopaedic conditions to enhance individualized care and welfare. Over 3 years, 123 chronically lame horses and 6 healthy control horses at an animal sanctuary underwent regular (every 3 months) comprehensive health assessments and...
Z Kelemen

Can cognitive reserve offset APOE-related Alzheimer's risk? A systematic review

7 months 1 week ago
Alzheimer's disease (AD) is a neurocognitive disorder that affects a significant part of the population. Its symptoms include progressive loss of memory and executive dysfunction. Genetic susceptibility to AD can be influenced by allele variants of the APOE gene. On the other hand, lifelong experiences such as educational attainment, occupational complexity, and leisure activities, known proxies for cognitive reserve (CR), may modulate gene expression, ultimately impacting AD susceptibility. In...
Sayonara Pereira da Silva

Start the engine of neuroregeneration: A mechanistic and strategic overview of direct astrocyte-to-neuron reprogramming

7 months 1 week ago
The decline of adult neurogenesis and neuronal function during aging underlies the onset and progression of neurodegenerative diseases such as Alzheimer's disease. Conventional therapies, including neurotransmitter modulators and antibodies targeting pathogenic proteins, offer only symptomatic improvement. As the most abundant glial cells in the brain, astrocytes outnumber neurons nearly fivefold. However, their proliferative and transdifferentiation potential renders them ideal candidates for...
Hangyuan Jiang

The potential role of aryl hydrocarbon receptor in Alzheimer's disease: Protective or detrimental

7 months 1 week ago
Alzheimer's disease (AD) is the main cause of dementia in the old-age population worldwide. AD is a progressive brain neurodegenerative disease due to genetic and environmental factors that induce the accumulation of intracellular hyperphosphorylated tau protein and extracellular amyloid protein (Aβ). Particularly, cholinergic neurons in the prefrontal cortex and hippocampus are mainly affected in AD, resulting in cognitive impairment and memory dysfunction. Therefore, restoration of cholinergic...
Hayder M Al-Kuraishy

The lncRNA Gas5 is an activity-responsive scaffold that mediates cAMP-dependent synaptic plasticity

7 months 1 week ago
Changes in the transcriptome are critical in shaping the structural plasticity of neurons, which underpins learning and long-term memory storage. Here, we explored the effect of two opposing, plasticity-associated pathways-cAMP second-messenger signaling and metabotropic glutamate receptor (mGluR1 and mGluR5) signaling-on the transcriptome in hippocampal neurons and how these pathways operate in distinct and coordinated manners to induce structural changes. Integration of transcriptome data and...
Kaushik Chanda