Partial reduction of microglia does not affect tau pathology in aged mice

Area of Science:

• Neuroscience
• Immunology
• Pathology

Background:

• Brain inflammation is implicated in Alzheimer's disease (AD), potentially driving tau protein accumulation and spread.
• Microglia, the brain's immune cells, play a central role in neuroinflammation.
• Understanding microglial involvement is crucial for developing effective AD therapies.

Purpose of the Study:

• To investigate how altering microglia numbers affects tau pathology in a mouse model of Alzheimer's disease.
• To assess the impact of microglial reduction on neuronal degeneration, astrocyte activity, and blood vessel changes.
• To determine if targeting microglia can mitigate tau protein accumulation and associated neuropathology.

Main Methods:

• Utilized PLX3397, a colony-stimulating factor 1 receptor (CSF1R) inhibitor, to deplete microglia in tau-overexpressing mice.
• Administered PLX3397 or a control diet for 3 months to 12-month-old mice.
• Analyzed changes in tau burden, brain atrophy, blood vessel morphology, and astrocyte activation via microscopy and histology.

Main Results:

• PLX3397 treatment reduced microglial numbers by 30% but did not alter tau burden, cortical atrophy, or blood vessel morphology.
• Disease-associated microglial gene expression remained elevated despite microglial reduction.
• Unexpectedly, PLX3397 treatment led to increased expression of CD68 and Tgf1β.

Conclusions:

• Modulating microglial populations may not be a sufficient strategy to reduce tau pathology in Alzheimer's disease.
• Higher PLX3397 doses or earlier intervention might be necessary for therapeutic effects.
• Further research is needed to elucidate the specific roles of microglial changes in the Alzheimer's disease process.