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Human-rodent chimeric CNS models provide a unique platform for investigating human-specific aspects of neurodegeneration within the physiological environment of the living CNS. These models are generated by transplanting human pluripotent…
Astrocytes and APOE are strongly implicated in Alzheimer's disease (AD), yet the impact of astrocytes carrying different APOE variants on AD hallmarks remains incompletely understood. Here, we generate a chimeric…
Alzheimer's disease typically unfolds within an aging brain, where astrocytic transcriptional programs are extensively remodeled. A recent study by Choi and colleagues shows that reinstating an aging-dependent Sox9-MEGF10 axis restores…
Astrocytes play crucial roles in central nervous system homeostasis, regulating neuronal and synaptic activity, modulating immune responses, and preserving the integrity of the blood-brain barrier. Recent genetic, transcriptomic, and proteomic…
The major genetic risk factor for Alzheimer's disease (AD), APOE4, accelerates beta-amyloid (Aβ) plaque formation, but whether this is caused by APOE expressed in microglia or astrocytes is debated. We…
The hippocampus is a brain area linked to cognition. The mechanisms that maintain cognitive activity in humans are poorly understood. Centenarians display extreme longevity which is generally accompanied by better…
Lee et al.1 report that loss of the Alzheimer's disease risk factor SORL1 results in neuron-specific reduction in APOE and CLU, altered lipid homeostasis, and increased Aβ levels and phosphorylated…
Neuronal cell loss is a defining feature of Alzheimer's disease (AD), but the underlying mechanisms remain unclear. We xenografted human or mouse neurons into the brain of a mouse model…
Astrocytes constitute a large part of the brain cell mass and play essential functions in the central nervous system. They provide trophic and metabolic support to neurons, regulate synapse formation,…
The evolution of the nervous system progressed through cellular diversification and specialization of functions. Conceptually, the nervous system is composed of electrically excitable neuronal networks connected by chemical synapses and…
Background: Increasing evidence for a direct contribution of astrocytes to neuroinflammatory and neurodegenerative processes causing Alzheimer's disease comes from molecular and functional studies in rodent models. However, these models may…
Abstract Astrocytes perform a wide variety of essential functions defining normal operation of the nervous system and are active contributors to the pathogenesis of neurodegenerative disorders such as Alzheimer’s among…
Although genetics highlights the role of microglia in Alzheimer's disease, one-third of putative Alzheimer's disease risk genes lack adequate mouse orthologs. Here we successfully engraft human microglia derived from embryonic…
Background: Astrocytes, also called astroglia, maintain homoeostasis of the brain by providing trophic and metabolic support to neurons. They recycle neurotransmitters, stimulate synaptogenesis and synaptic neurotransmission, form part of the…
The mitochondrial intramembrane rhomboid protease PARL has been implicated in diverse functions in vitro, but its physiological role in vivo remains unclear. Here we show that Parl ablation in mouse…
Tetraspanins (Tspan) are transmembrane proteins with important scaffold and signalling functions. Deletions of Tetraspanin 6 (Tspan6) gene, a member of the tetraspanin family, have been reported in patients with Epilepsy…
Background: The mechanisms behind Aβ-peptide accumulation in non-familial Alzheimer's disease (AD) remain elusive. Proteins of the tetraspanin family modulate Aβ production by interacting to γ-secretase. Methods: We searched for tetraspanins…
Human pluripotent stem cells (PSCs) provide a unique entry to study species-specific aspects of human disorders such as Alzheimer's disease (AD). However, in vitro culture of neurons deprives them of…
Cruchaga et al. 1 recently showed that:(1) variants in the phospholipase D3 (PLD3) gene confer increased risk for the development of Alzheimer’s disease (AD);(2) PLD3 expression is decreased in patients…
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