A new study highlighted the role of the microglial immune receptor TREM2 in protecting against age-related myelin degeneration, a key factor in neurodegenerative conditions such as Alzheimer's disease. Researchers found that a deficiency in TREM2 aggravated and accelerated the loss of myelin in the brain's striatum, further supporting the growing evidence of its critical role in maintaining brain health during aging.

Aging is known to lead to a slow but steady decline in myelin, the insulating material that surrounds nerve fibers and is vital for proper neural function. Myelin degeneration has been linked to neurodegenerative disorders, and white matter damage is often an early sign of such diseases.

In the study, published in Acta Neuropathologica Communications, researchers focused on how TREM2, a receptor found primarily on microglial cells in the brain, may be essential for modulating the processes of demyelination and remyelination (repairing damaged myelin) in aging brains.

Using genetically modified mice that lacked TREM2, the researchers discovered a significant worsening of age-related myelin degeneration. In the striatum, a brain region important for motor and cognitive functions, TREM2-deficient mice experienced accelerated myelin loss compared with their wild-type counterparts. This led to increased levels of myelin debris and axonal damage, both indicators of chronic neurodegeneration.

One of the major findings was that TREM2 was essential for clearing myelin debris. Microglia, the brain's immune cells, normally phagocytose (engulf and digest) damaged myelin. However, in the absence of TREM2, this process was impaired, resulting in a buildup of myelin debris and a failure to initiate effective repair. Without proper debris clearance, the oligodendrocyte precursor cells responsible for generating new myelin were unable to mature, leading to sustained myelin deficits.

The study also found that TREM2 played a role in controlling the cellular stress response. Microglia lacking TREM2 exhibited increased endoplasmic reticulum stress, which worsened their ability to manage the lipid burden from accumulating myelin debris. This stress led to the formation of lipid droplets, a sign of microglial dysfunction, which may contribute to long-term damage and impaired myelin repair.

The researchers hope their work will lead to further exploration of TREM2's role in aging and neurodegeneration, and how boosting TREM2 activity may be a potential approach to enhance myelin repair and slow disease progression.

There were no conflicts of interest reported by the authors of this study.