What you carry at this position in your DNA and what research says about it.
Alzheimer's Risk: 10/10 evidence, 29 publications.
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Sample genotype (not yours): C/C
Lower Risk of Alzheimer's Disease and Dementia
The C/C genotype is associated with a typical risk of cognitive decline and neurodegenerative diseases.
What this genotype means: Typical risk of cognitive decline; Better late-life verbal memory; Slightly higher risk of type 2 diabetes.
Sample genotype (not yours): C/T
Moderately Increased Risk of Alzheimer's Disease
The C/T genotype is linked to a moderately higher risk of developing Alzheimer's disease and other forms of dementia.
What this genotype means: Moderately higher risk of Alzheimer's disease; Slightly higher LDL cholesterol; Slightly lower risk of type 2 diabetes.
Sample genotype (not yours): T/T
Elevated Risk of Alzheimer's Disease and Dementia
The T/T genotype is associated with an elevated risk of cognitive decline, Alzheimer's disease, and frontotemporal dementia.
What this genotype means: Elevated risk of Alzheimer's disease and dementia; Higher circulating LDL cholesterol; Lower risk of type 2 diabetes.
Gene function and biological role
Gene Function: NECTIN2, also known as PVRL2, encodes a cell adhesion molecule that plays a vital role in organizing cell junctions and mediating cell-to-cell interactions. In the brain, NECTIN2 is highly expressed in the cerebral cortex and is involved in synaptic function and blood-brain barrier integrity. Because of its close physical proximity to the APOE gene on chromosome 19, genetic variations in NECTIN2 are frequently inherited alongside APOE variants [1]. This genetic linkage makes NECTIN2 a major locus of interest in neurodegenerative research [2].
Variant Impact: The rs6857 variant is located in the 3' untranslated region of the NECTIN2 gene, where it alters a binding site for regulatory microRNAs. This regulatory change is strongly linked to altered levels of apolipoprotein E and amyloid-beta deposition in the brain [3]. Consequently, rs6857 is one of the most prominent non-APOE markers associated with late-onset Alzheimer's disease and cognitive aging [4].
Key Insight: This variant acts as a genetic trade-off, where the allele that increases the risk of Alzheimer's disease and dementia actually lowers the risk of type 2 diabetes and body fat percentage.
Location: NECTIN2. Chromosome 19 · 19q13.32 · 44.9 Mb
Estimated prevalence by population
Global 76.6%; European 70.4%; African 88.0%; East Asian 80.0%; South Asian 74.5%; Americas 80.4%; Ashkenazi 73.2%; Finnish 65.7%; Middle Eastern 87.5%; Amish 73.5%.
Estimated CC genotype frequency.
Global 21.6%; European 27.0%; African 11.6%; East Asian 18.9%; South Asian 23.6%; Americas 18.5%; Ashkenazi 24.7%; Finnish 30.7%; Middle Eastern 12.1%; Amish 24.4%.
Estimated CT genotype frequency.
Global 1.8%; European 2.6%; African 0.4%; East Asian 1.1%; South Asian 1.9%; Americas 1.1%; Ashkenazi 2.1%; Finnish 3.6%; Middle Eastern 0.4%; Amish 2.0%.
Estimated TT genotype frequency.
Showing effects for C/C genotype
Neurology & Mental Health
Neurodegenerative Diseases
Alzheimer's Disease. Evidence: 10/10. Source: PMID 23419831. Typical Risk.
Dementia. Evidence: 10/10. Source: PMID 25188341. Typical Risk.
Memory, Learning & Attention
Memory Performance. Evidence: 8/10. Source: PMID 25648963. Higher Performance.
Cardiovascular & Metabolic
Diabetes & Glycemic Traits
Type 2 Diabetes. Evidence: 8/10. Source: PMID 27189021. ~1.12x Risk.
Lipids & Cholesterol
LDL Cholesterol. Evidence: 9/10. Source: PMID 31719535. Typical.
Showing effects for C/T genotype
Alzheimer's Disease. Evidence: 10/10. Source: PMID 23419831. ~1.27x Risk.
Dementia. Evidence: 10/10. Source: PMID 25188341. Increased Risk.
Memory Performance. Evidence: 8/10. Source: PMID 25648963. Typical.
Type 2 Diabetes. Evidence: 8/10. Source: PMID 27189021. Typical Risk.
LDL Cholesterol. Evidence: 9/10. Source: PMID 31719535. Slightly Elevated.
Showing effects for T/T genotype
Alzheimer's Disease. Evidence: 10/10. Source: PMID 23419831. Elevated Risk.
Dementia. Evidence: 10/10. Source: PMID 25188341. Elevated Risk.
Memory Performance. Evidence: 8/10. Source: PMID 25648963. Lower Performance.
Type 2 Diabetes. Evidence: 8/10. Source: PMID 27189021. Lower Risk.
LDL Cholesterol. Evidence: 9/10. Source: PMID 31719535. Elevated.
What this genotype means for the people who carry it
Sample genotype: CC (Homozygous)
The C/C genotype is the most common globally and is associated with a lower risk of developing late-onset Alzheimer's disease and frontotemporal dementia compared to carrying the T allele [1] [2]. Research indicates that individuals with this genotype tend to have lower levels of amyloid-beta plaque deposition in the brain [3]. Additionally, studies have linked this genotype to better verbal declarative memory performance in late life [4]. However, there is a minor trade-off, as the C allele is associated with a slightly higher body mass index and a modest increase in type 2 diabetes risk [5]. Overall, this genetic profile is highly favorable for long-term brain health and cognitive preservation. Maintaining a healthy lifestyle can further support cognitive resilience. Regular physical exercise and a balanced diet are excellent ways to promote brain health regardless of genetic background.
Typical risk of cognitive decline; Better late-life verbal memory; Slightly higher risk of type 2 diabetes.
Sample genotype: CT (Heterozygous)
The heterozygous C/T genotype is linked to a moderate increase in susceptibility to neurodegenerative conditions. Large-scale genetic studies have demonstrated a moderate increase in the risk of late-onset Alzheimer's disease and frontotemporal dementia for carriers of this allele [1] [2]. This risk is partly driven by the strong genetic linkage between NECTIN2 and the neighboring APOE gene region [3]. On a physiological level, this variant is associated with higher levels of amyloid-beta accumulation in the brain [4]. Conversely, carriers of the T allele tend to have a slightly lower body mass index and a reduced risk of type 2 diabetes compared to those with the C/C genotype [5]. Engaging in mentally stimulating activities and managing cardiovascular risk factors can help support cognitive health. Regular check-ups with a healthcare provider can assist in monitoring overall wellness.
Moderately higher risk of Alzheimer's disease; Slightly higher LDL cholesterol; Slightly lower risk of type 2 diabetes.
Sample genotype: TT (Homozygous)
The homozygous T/T genotype is relatively rare and carries the highest genetic risk at this locus for neurodegenerative disorders. Having two copies of the T allele is strongly associated with an increased risk of late-onset Alzheimer's disease and frontotemporal dementia [1] [2]. This genetic variant is linked to accelerated amyloid-beta plaque deposition, a hallmark of Alzheimer's pathology [3]. Furthermore, individuals with this genotype are more likely to exhibit higher circulating levels of LDL cholesterol and an increased risk of metabolic syndrome [4] [5]. On the positive side, this genotype is associated with a lower risk of developing type 2 diabetes and a lower average body mass index [6]. Prioritizing cardiovascular health through regular exercise and a heart-healthy diet is particularly beneficial for individuals with this profile. These lifestyle measures can help mitigate some of the metabolic and cognitive risks associated with this genotype.
Elevated risk of Alzheimer's disease and dementia; Higher circulating LDL cholesterol; Lower risk of type 2 diabetes.
Variants with shared genetic architecture
rs6859 · NECTIN2 Gene · Chr 19 · Alzheimer's Disease Risk
rs7254892 · NECTIN2 Gene · Chr 19 · Cholesterol and Brain Health
rs41289512 · NECTIN2 Gene · Chr 19 · Alzheimer's and Cholesterol
Transethnic genome-wide scan identifies novel Alzheimer's disease loci.
A Genome-Wide Association Study of Metabolic Syndrome in the Taiwanese Population.
Content updated August 2026.
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