What you carry at this position in your DNA and what research says about it.
Alzheimer's Disease Risk: 10/10 evidence, 36 publications.
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Sample genotype (not yours): G/G
Typical Risk of Alzheimer's and Cognitive Decline
Carrying two copies of the G allele is associated with typical brain health and standard lipid levels. This genotype does not carry the risk-associated A allele linked to accelerated cognitive decline.
What this genotype means: Typical risk of Alzheimer's disease; Standard cognitive aging pattern; Typical LDL and triglyceride levels.
Sample genotype (not yours): A/A
Significantly Increased Risk of Alzheimer's and Cognitive Decline
Carrying two copies of the A allele is associated with a significantly higher risk of Alzheimer's disease and Lewy body dementia. This genotype is also linked to accelerated cognitive decline and elevated cholesterol.
What this genotype means: Significantly elevated risk of Alzheimer's disease; Markedly increased risk of Lewy body dementia; Elevated LDL cholesterol and triglycerides.
Sample genotype (not yours): G/A
Increased Risk of Alzheimer's and Cognitive Decline
Carrying one copy of the A allele is linked to a higher risk of developing Alzheimer's disease and Lewy body dementia. It is also associated with elevated LDL cholesterol and faster cognitive aging.
What this genotype means: Elevated risk of Alzheimer's disease; Increased risk of Lewy body dementia; Higher LDL cholesterol and triglycerides.
Gene function and biological role
Gene Function: APOE encodes apolipoprotein E, a major cholesterol carrier in the brain and peripheral tissues. It plays a critical role in lipid transport, neurobiology, and the clearance of beta-amyloid proteins. Variations in this gene are the most significant genetic determinants of late-onset Alzheimer's disease [1]. The gene is also heavily implicated in cardiovascular health, lipid levels, and other neurodegenerative conditions like Lewy body dementia [2].
Variant Impact: Located within an intron of the APOE gene, rs769449 is a common genetic marker. Tight linkage disequilibrium connects this marker with the well-known APOE e4 allele, a major driver of cognitive decline [3]. The minor A allele of this variant is associated with elevated levels of phosphorylated tau and total tau proteins in cerebrospinal fluid [4]. Conversely, the major G allele is linked to higher levels of beta-amyloid 1-42 in cerebrospinal fluid, indicating better clearance of amyloid plaques from the brain [5].
Key Insight: The rs769449 variant is tightly linked to the APOE e4 allele, making it a strong proxy for genetic Alzheimer's risk. It also influences cardiovascular health by altering LDL cholesterol and triglyceride levels.
Location: APOE. Chromosome 19 · 19q13.32 · 44.9 Mb
Estimated prevalence by population
Global 84.1%; European 79.1%; African 95.8%; East Asian 83.8%; South Asian 85.5%; Americas 85.3%; Ashkenazi 83.4%; Finnish 68.1%; Middle Eastern 94.6%; Amish 74.9%.
Estimated GG genotype frequency.
Global 15.0%; European 19.7%; African 4.2%; East Asian 15.5%; South Asian 13.9%; Americas 14.1%; Ashkenazi 15.8%; Finnish 28.8%; Middle Eastern 5.3%; Amish 23.3%.
Estimated GA genotype frequency.
Global 0.9%; European 1.2%; African < 0.1%; East Asian 0.7%; South Asian 0.6%; Americas 0.6%; Ashkenazi 0.8%; Finnish 3.0%; Middle Eastern 0.1%; Amish 1.8%.
Estimated AA genotype frequency.
Showing effects for G/G genotype
Neurology & Mental Health
Neurodegenerative Diseases
Alzheimer's Disease. Evidence: 10/10. Source: PMID 30636644. Typical Risk.
Lewy Body Dementia. Evidence: 8/10. Source: PMID 33589841. Typical Risk.
Cognitive Performance
Cognitive Decline. Evidence: 8/10. Source: PMID 24468470. Typical Rate.
Memory, Learning & Attention
Memory Performance. Evidence: 6/10. Source: PMID 28800603. Typical Performance.
Cardiovascular & Metabolic
Lipids & Cholesterol
LDL Cholesterol. Evidence: 10/10. Source: PMID 29507422. Typical Levels.
Triglycerides. Evidence: 8/10. Source: PMID 29507422. Typical Levels.
Hypertension
Diastolic Blood Pressure. Evidence: 6/10. Source: PMID 33230300. Slightly Higher.
Showing effects for A/A genotype
Alzheimer's Disease. Evidence: 10/10. Source: PMID 30636644. Highly Increased Risk.
Lewy Body Dementia. Evidence: 8/10. Source: PMID 33589841. Highly Increased Risk.
Cognitive Decline. Evidence: 8/10. Source: PMID 24468470. Highly Accelerated.
Memory Performance. Evidence: 6/10. Source: PMID 28800603. Lowest Performance.
LDL Cholesterol. Evidence: 10/10. Source: PMID 29507422. Highly Increased Levels.
Triglycerides. Evidence: 8/10. Source: PMID 29507422. Highly Increased Levels.
Diastolic Blood Pressure. Evidence: 6/10. Source: PMID 33230300. Slightly Lower.
Showing effects for G/A genotype
Alzheimer's Disease. Evidence: 10/10. Source: PMID 30636644. Increased Risk.
Lewy Body Dementia. Evidence: 8/10. Source: PMID 33589841. ~2.3x Increased Risk.
Cognitive Decline. Evidence: 8/10. Source: PMID 24468470. Accelerated Decline.
Memory Performance. Evidence: 6/10. Source: PMID 28800603. Reduced Performance.
LDL Cholesterol. Evidence: 10/10. Source: PMID 29507422. Increased Levels.
Triglycerides. Evidence: 8/10. Source: PMID 29507422. Increased Levels.
Diastolic Blood Pressure. Evidence: 6/10. Source: PMID 33230300. Typical.
What this genotype means for the people who carry it
Sample genotype: GG (Homozygous)
Representing the most common genetic profile globally, this genotype is found in about 91.6% of the population. Standard clearance of beta-amyloid proteins from the brain is typical for these individuals, helping protect against plaque buildup [1]. Clinical studies show they have a typical risk profile for late-onset Alzheimer's disease and Lewy body dementia compared to carriers of the A allele [2]. Cardiovascular health is also supported by standard levels of LDL cholesterol and triglycerides [3]. Cognitive performance, particularly verbal memory, tends to remain stable during aging in individuals with this profile [4].
Typical risk of Alzheimer's disease; Standard cognitive aging pattern; Typical LDL and triglyceride levels.
Sample genotype: AA (Homozygous)
Possessing two copies of the minor A allele strongly associates this profile with the homozygous APOE e4 state. An elevated risk of developing late-onset Alzheimer's disease and Lewy body dementia is well-documented for this genotype [1]. Marked accumulation of phosphorylated tau and total tau proteins in the brain characterizes this genetic profile [2]. Reduced clearance of beta-amyloid leads to lower levels in cerebrospinal fluid and higher plaque deposition [3]. Cardiovascular risk markers, including LDL cholesterol, total cholesterol, and triglycerides, are typically elevated in these individuals [4]. Cognitive decline, particularly in memory performance, tends to occur at an accelerated rate during late life [5].
Significantly elevated risk of Alzheimer's disease; Markedly increased risk of Lewy body dementia; Elevated LDL cholesterol and triglycerides.
Sample genotype: GA (Heterozygous)
Carrying one copy of the minor A allele tightly links this profile to the APOE e4 risk variant. Research indicates that having one A allele increases the risk of developing Alzheimer's disease and Lewy body dementia [1]. Elevated levels of phosphorylated tau and total tau proteins, which are key biomarkers of neurodegeneration, are commonly observed [2]. Additionally, reduced clearance of amyloid plaques from the brain is suggested by lower levels of beta-amyloid 1-42 in cerebrospinal fluid [3]. Lipid metabolism is also affected, leading to higher levels of LDL cholesterol, total cholesterol, and triglycerides [4]. Memory performance, especially verbal recall, may decline more rapidly with age [5].
Elevated risk of Alzheimer's disease; Increased risk of Lewy body dementia; Higher LDL cholesterol and triglycerides.
Variants with shared genetic architecture
rs429358 · APOE Gene · Chr 19 · Alzheimer's Disease Risk
rs7412 · APOE Gene · Chr 19 · Cholesterol and Heart Risk
rs449647 · APOE Gene · Chr 19 · Alzheimer Risk and ApoE Levels
Genome-wide analysis of genetic predisposition to Alzheimer's disease and related sex disparities.
Genetic susceptibility to accelerated cognitive decline in the US Health and Retirement Study.
Genome-wide association study identifies APOE locus influencing plasma p-tau181 levels.
A large electronic-health-record-based genome-wide study of serum lipids.
Content updated August 2026.
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