TREM2 and Alzheimer’s Disease Risk

Key takeaways:
~ TREM2 activates autophagy in microglial cells, which clean ups cellular debris in the brain.
~ Genetic variants in TREM2 cause increased Alzheimer’s risk.
~ Understanding your risk of Alzheimer’s disease can help you prioritize your best ways of preventing Alzheimer’s.

TREM2, Microglia, and Alzheimer’s risk:

There are two types of Alzheimer’s:

• Early-onset, familial Alzheimer’s disease is caused by rare mutations in the APP, PSEN1, and PSEN2 genes.
• A late-onset form of dementia is associated with several genetic variants, including the APOE gene and the TREM2 gene. If you want to know your APOE genotype, you can check it out here.

Genetics research over the past decade has highlighted the importance of the immune response as central to Alzheimer’s disease. Most genetic risk factors discovered for Alzheimer’s involve the brain’s immune system.[ref]

Microglia: brain immune cells

Microglia cells are an important cell type in the brain and spinal cord. Microglia are the primary immune defense cells that fight off pathogens in the brain. But they are also critical for responding to cellular stress in the brain’s neurons and cleaning up cellular debris.

The blood-brain barrier does a good job of keeping most bacteria out of the brain. In turn, the blood-brain barrier also blocks the rest of the body’s immune cells, such as white blood cells, from entering the brain. Thus, microglia are the brain’s resident immune cells. When activated, microglia release cytokines.

Within different regions of the brain, up to 16% of the cells may be microglia. Microglia respond to and interact with other molecules in their environment, such as pathogen-associated molecules (PAMPs) and cell-damaging molecules in the brain (DAMPs).[ref]

Like many immune system responses, microglial activation can be a double-edged sword. Initially, activation of microglia can help clean up cellular debris. However, overactivation leads to the secretion of inflammatory cytokines that can damage neurons.[ref]

The TREM2 gene and Alzheimer’s

The TREM2 gene encodes a receptor on microglia that receives signals from nearby neurons and then activates several important functions of microglia. For example, TREM2 is essential for activating autophagy or phagocytosis in microglial cells, which is necessary to clear cellular debris in the brain.[ref]

TREM2 can be activated by several different molecules, including APOE, bacterial lipopolysaccharides, and amyloid-β. So you can see how it is at an integral crossroads in how the brain responds to several important molecules in Alzheimer’s pathogenesis.

Lifehacks:

Diet, exercise, and a healthy lifestyle are all important in preventing Alzheimer’s disease. Seriously- I know it sounds like just the same old general advice, but research studies do show that all of the lifestyle factors do matter in Alzheimer’s disease.

Binge drinking and the oral microbiome:
A new study shows that binge drinking causes a shift in the oral microbiome. Excessive ethanol affects the oral microbiome and couples with increased permeability to the blood-brain barrier, possibly increasing the ability of bacteria to reach the brain.[ref]

Learn more about the research on the oral microbiome and Alzheimer’s.

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