Thread by @BrainMindRes

People with #dementia have protein build-up in astrocytes that may trigger abnormal antiviral activity and memory loss. Abnormal immune activity in non-neuronal brain cells called astrocytes is sufficient to cause cognitive deficits in dementia.

#2. The discovery could lead to new treatments that reduce excess immune activity in astrocytes and their detrimental effects on other brain cells and cognition.

#3. To understand the causes of memory loss at the molecular level, analyzed gene expression and found high levels of antiviral gene activities, even though no virus was present in the brain. Astrocytes produced excessive amounts of immune messengers called chemokines, which

#4. can activate CXCR3 chemokine receptors typically found on infiltrating immune cells. To their surprise, the team discovered that CXCR3 receptor levels were elevated in hippocampal neurons, and that excessive CXCR3 receptor activity made neurons "hyperactive".

#5. Blocking CXCR3 reduced neuronal firing in individual neurons & eliminating CXCR3 in mice by genetic engineering alleviated cognitive deficits caused by astrocytic TDP-43 build-up. These experiments demonstrate that impaired astrocytes can have a detrimental role in dementia.

#6. For effective therapeutics, need to consider astrocytes along with neurons. Drugs that target the identified immune pathways might help improve cognitive function in people with dementia. She noted that scientists are already testing CXCR3 blockers to treat arthritis and

#7. other inflammatory conditions in clinical trials. These drugs could be tested and potentially repurposed for dementia. This study may also provide insights into how antiviral immune responses can cause cognitive dysfunction.

#8. Previous research has linked viral infections to Alzheimer's disease and to long-term neurocognitive effects such as memory loss and brain fog.

#9. Abnormal immune activity in astrocytes might contribute to these cognitive effects as well as increase individuals' susceptibility to viral infections, which could further worsen brain health and promote some cases of dementia. ( Weill Cornell Medicine)