Study links astrocytic TDP-43 dysfunction to cognitive decline in dementia: Unlocking potential therapeutic strategies TDP43 Astrocytes Neurodegenerative CXCR3 Chemokines MemoryLoss BrainResearch Alzheimers lDementia ScienceAdvances
Reviewed by Danielle Ellis, B.Sc.Apr 20 2023 People with dementia have protein build-up in astrocytes that may trigger abnormal antiviral activity and memory loss, according to a preclinical study by a team of Weill Cornell Medicine investigators.
"Astrocyte dysfunction alone can drive memory loss, even when neurons and other cells are otherwise healthy," said co-senior author Dr. Anna Orr, the Nan and Stephen Swid Assistant Professor of Frontotemporal Dementia Research in the Feil Family Brain and Mind Research Institute and a member of the Helen and Robert Appel Alzheimer's Disease Research Institute at Weill Cornell Medicine.
When the investigators, including first author Dr. Avital Licht-Murava, a former postdoctoral associate in the Orr lab, examined tissue samples from deceased individuals who were diagnosed with either Alzheimer's disease or frontotemporal dementia, they found an accumulation of a protein called TDP-43 in astrocytes within the hippocampus, a brain region crucial for memory.
"Blocking CXCR3 reduced neuronal firing in individual neurons and eliminating CXCR3 in mice by genetic engineering alleviated cognitive deficits caused by astrocytic TDP-43 build-up," Dr. Adam Orr said. These experiments demonstrate that impaired astrocytes can have a detrimental role in dementia, he said."For effective therapeutics, we need to consider astrocytes along with neurons," Dr. Anna Orr said.
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