TREM2 rs75923636: Understanding the p.R62H Variant and Alzheimer's
The rs75923636 variant in the TREM2 gene, often referred to as p.R62H, is a rare genetic change associated with an increased risk of developing Alzheimer's disease. This variant affects the function of microglia, the immune cells of the brain, which play a critical role in maintaining neural health.
What each genotype means
Typical TREM2 genotype
This is the most common genotype for this position in the TREM2 gene. It is considered the reference sequence and is not associated with the increased Alzheimer's disease risk linked to the R62H variant.
This is the predominant genotype found in the vast majority of the global population.
Increased Alzheimer's risk variant
This genotype represents the heterozygous state for the p.R62H variant (also referred to as the R62H mutation). Research indicates that this variant may affect TREM2 protein function and splicing, and it is statistically associated with an increased risk of developing late-onset Alzheimer's disease.
This variant is rare, carried by approximately 1% of individuals of European ancestry.
Homozygous risk variant
This genotype indicates that both copies of the TREM2 gene carry the R62H variant. While the heterozygous state is more commonly studied in the context of Alzheimer's risk, the presence of two copies of this variant may further influence TREM2-related biological pathways, though clinical data on this specific homozygous state is limited.
This genotype is extremely rare in the general population.
What is the rs75923636 Variant?
The rs75923636 variant is a single nucleotide polymorphism (SNP) located within the TREM2 gene on chromosome 6. In genetic terms, this specific change results in an amino acid substitution where arginine is replaced by histidine at position 62 of the protein, commonly denoted as p.R62H. Because this change occurs in the coding region of the gene, it can alter the structure and function of the resulting protein. Scientists study this variant because it is considered a rare genetic factor that may influence an individual's susceptibility to neurodegenerative conditions. It is important to note that having this variant does not mean an individual will develop a disease; rather, it is one of many factors that researchers investigate to understand the complex biological pathways involved in brain aging and cognitive decline.
The Role of the TREM2 Gene
The TREM2 gene provides instructions for making a protein called Triggering Receptor Expressed on Myeloid cells 2. This protein is primarily found on the surface of microglia, which are specialized immune cells residing in the central nervous system. Microglia act as the brain's 'cleanup crew,' responsible for identifying and removing cellular debris, misfolded proteins, and other harmful substances. By facilitating phagocytosis—the process of engulfing and digesting these materials—TREM2 helps regulate the inflammatory response and supports overall neuronal health. When the TREM2 protein is altered by variants like p.R62H, its ability to sense and respond to damage may be impaired. This dysfunction can lead to a less effective immune response in the brain, potentially contributing to the accumulation of amyloid-beta plaques or other pathological features associated with Alzheimer's disease.
Research and Evidence Strength
Research into the p.R62H variant has consistently identified it as a risk factor for Alzheimer's disease, though the evidence is considered moderate compared to more common genetic markers. Studies, including those published in journals like the New England Journal of Medicine and various genetic databases, have shown that individuals carrying this variant have a higher statistical likelihood of developing the condition compared to those without it. The odds ratio for this variant suggests a significant association, though it is often studied alongside other rare variants in the same gene, such as p.R47H. Because these variants are rare, researchers often pool data from large cohorts to achieve statistical significance. While the link between TREM2 dysfunction and neurodegeneration is well-supported in laboratory models, the exact clinical impact on an individual level remains a subject of ongoing scientific investigation.
Population Frequency
The rs75923636 variant is classified as a rare variant, meaning it is found at a very low frequency in the general population. Because it is rare, it is not typically included in standard, broad-spectrum genetic screening panels. Its distribution can also vary significantly across different ancestral backgrounds, which is a common feature of rare genetic variants. Researchers rely on large-scale sequencing projects, such as gnomAD, to estimate how often this variant appears in diverse groups. Due to its low frequency, many studies have limited power to draw definitive conclusions about its prevalence in specific populations, and further research is needed to fully map its occurrence globally. The rarity of the variant underscores the importance of large, collaborative international studies in understanding its role in human health.
What This Information Means for You
Learning about a genetic variant like rs75923636 can be informative, but it is essential to interpret such findings within the context of overall health. This variant is a risk factor, not a diagnostic tool; it cannot predict with certainty whether an individual will develop Alzheimer's disease. Many people who carry this variant may never develop the condition, and many who develop the condition do not carry this variant. If you have received information about your genetic status regarding this SNP, it is best to discuss the findings with a healthcare professional or a genetic counselor who can provide context based on your personal and family medical history. Avoid making medical decisions based solely on genetic data. Focus instead on established lifestyle factors that support brain health, such as regular physical activity, a balanced diet, and cognitive engagement, which are beneficial regardless of your genetic profile.
How common is this variant?
The rs75923636 variant is rare across most global populations, appearing at very low frequencies in genomic databases.
Frequently asked questions
Does having the rs75923636 variant mean I will get Alzheimer's?
No, having this variant does not mean you will develop Alzheimer's disease. It is a risk factor that statistically increases the likelihood of the condition, but it is not a definitive cause.
Should I get tested for the TREM2 p.R62H variant?
Genetic testing for this variant is not currently recommended for the general public. It is typically only relevant in specific research contexts or when discussed with a medical professional regarding family history.
Is there a treatment for people with the TREM2 p.R62H variant?
There are currently no specific treatments or medications targeted at individuals based on this genetic variant. Research into drugs that modulate TREM2 function is ongoing, but these are not yet standard clinical practice.
How does this variant compare to the APOE e4 allele?
The APOE e4 allele is a much more common and well-established genetic risk factor for late-onset Alzheimer's disease. The TREM2 p.R62H variant is much rarer and represents a different biological pathway involving the immune system.
Sources & further reading
Educational information only, last refreshed 9/24/2026. Not medical advice — these associations describe population statistics, not individual predictions.
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