Astrocytic autophagy plasticity modulates Aβ clearance and cognitive function in Alzheimer's disease.

Background: Astrocytes, one of the most resilient cells in the brain, transform into reactive astrocytes in response to toxic proteins such as amyloid beta (Aβ) in Alzheimer's disease (AD). However, reactive astrocyte-mediated non-cell autonomous neuropathological mechanism is not fully understood yet. We aimed our study to find out whether Aβ-induced proteotoxic stress affects the expression of autophagy genes and the modulation of autophagic flux in astrocytes, and if yes, how Aβ-induced autophagy-associated genes are involved Aβ clearance in astrocytes of animal model of AD.

Long-term inhibition of ODC1 in APP/PS1 mice rescues amyloid pathology and switches astrocytes from a reactive to active state.

Alzheimer's disease (AD) is characterized by the loss of memory due to aggregation of misphosphorylated tau and amyloid beta (Aβ) plaques in the brain, elevated release of inhibitory neurotransmitter gamma-aminobutyric acid (GABA) and reactive oxygen species from astrocytes, and subsequent neurodegeneration. Recently, it was found that enzyme Ornithine Decarboxylase 1 (ODC1) acts as a bridge between the astrocytic urea cycle and the putrescine-to-GABA conversion pathway in the brain of AD mouse models as well as human patients. In this study, we show that the long-term knockdown of astrocytic Odc1 in APP/PS1 animals was sufficient to completely clear Aβ plaques in the hippocampus while simultaneously switching the astrocytes from a detrimental reactive state to a regenerative active state, characterized by proBDNF expression.

Hypothalamic GABRA5-positive neurons control obesity via astrocytic GABA.

The lateral hypothalamic area (LHA) regulates food intake and energy balance. Although LHA neurons innervate adipose tissues, the identity of neurons that regulate fat is undefined. Here we show that GABRA5-positive neurons in LHA (GABRA5) polysynaptically project to brown and white adipose tissues in the periphery.

Visualizing reactive astrocyte-neuron interaction in Alzheimer's disease using 11C-acetate and 18F-FDG.

Reactive astrogliosis is a hallmark of Alzheimer's disease (AD). However, a clinically validated neuroimaging probe to visualize the reactive astrogliosis is yet to be discovered. Here, we show that PET imaging with 11C-acetate and 18F-fluorodeoxyglucose (18F-FDG) functionally visualizes the reactive astrocyte-mediated neuronal hypometabolism in the brains with neuroinflammation and AD.

Astrocytic urea cycle detoxifies Aβ-derived ammonia while impairing memory in Alzheimer's disease.

Alzheimer's disease (AD) is one of the foremost neurodegenerative diseases, characterized by beta-amyloid (Aβ) plaques and significant progressive memory loss. In AD, astrocytes are proposed to take up and clear Aβ plaques. However, how Aβ induces pathogenesis and memory impairment in AD remains elusive.

Genomics: New Light on Alzheimer's Disease Research.

Alzheimer's disease (AD) is a progressive neurodegenerative disease that represents a major cause of death in many countries. AD is characterized by profound memory loss, disruptions in thinking and reasoning, and changes in personality and behavior followed by malfunctions in various bodily systems. Although AD was first identified over 100 years ago, and tremendous efforts have been made to cure the disease, the precise mechanisms underlying the onset of AD remain unclear.