What you carry at this position in your DNA and what research says about it.
Cognitive Decline Risk: 9/10 evidence, 23 publications.
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Sample genotype (not yours): C/C
Typical Memory Performance and Lower Alzheimer's Risk
A common genetic profile is associated with typical age-related memory retention and a lower risk of developing Alzheimer's disease. This baseline combination also correlates with healthy lipid levels and typical brain structure over time.
What this genotype means: Stronger verbal memory performance; Lower risk of late-life dementia; Typical brain structure preservation.
Sample genotype (not yours): C/T
Slightly Weaker Memory and Elevated Alzheimer's Risk
One copy of the T allele is linked to a moderate increase in the risk of age-related memory decline and Alzheimer's disease. This genetic profile is also associated with slightly higher triglyceride levels and accelerated brain aging.
What this genotype means: Moderate risk of age-related memory decline; Slightly elevated risk of Alzheimer's disease; Slightly higher triglyceride levels.
Sample genotype (not yours): T/T
Weaker Memory Performance and Higher Alzheimer's Risk
Two copies of the T allele are associated with a more pronounced risk of age-related memory decline and Alzheimer's disease. This profile also correlates with elevated triglyceride levels and accelerated structural brain changes.
What this genotype means: Weaker verbal memory performance in older age; Elevated risk of late-onset Alzheimer's disease; Higher circulating triglyceride levels.
Gene function and biological role
Gene Function: Mitochondrial protein import is mediated by the channel-forming translocase encoded by the TOMM40 gene [1]. Because brain cells rely heavily on mitochondrial energy production, disruptions in this pathway are closely linked to neurodegenerative processes [1]. Located on chromosome 19, this gene is situated adjacent to the APOE locus, a region highly associated with cognitive aging and dementia [2]. Studies indicate that TOMM40 variations contribute to late-life memory performance and cognitive decline [3]. Furthermore, structural brain changes such as hippocampal atrophy have been mapped to genetic variations within this locus [4].
Variant Impact: The rs157582 variant is an intronic single nucleotide polymorphism located within the TOMM40 gene. This genetic change is strongly associated with age-related verbal memory decline and the rate of cognitive aging [3]. Research shows that the variant allele alters susceptibility to late-onset Alzheimer's disease and influences the deposition of amyloid-beta plaques in the brain [5]. It also correlates with structural changes in the brain, specifically affecting the rate of hippocampal atrophy in older adults [4]. Beyond neurological traits, this variant has been linked to systemic lipid metabolism, influencing circulating triglyceride levels [6].
Key Insight: The TOMM40 gene can influence age-related memory decline and dementia risk independently of the well-known APOE e4 Alzheimer's risk allele.
Location: TOMM40. Chromosome 19 · 19q13.32 · 44.9 Mb
Estimated prevalence by population
Global 52.3%; European 62.0%; African 29.0%; East Asian 62.6%; South Asian 64.7%; Americas 54.2%; Ashkenazi 64.6%; Finnish 60.2%; Middle Eastern 71.1%; Amish 71.8%.
Estimated CC genotype frequency.
Global 38.4%; European 33.5%; African 49.7%; East Asian 33.1%; South Asian 31.4%; Americas 38.8%; Ashkenazi 31.6%; Finnish 34.8%; Middle Eastern 26.4%; Amish 25.9%.
Estimated CT genotype frequency.
Global 9.3%; European 4.5%; African 21.3%; East Asian 4.4%; South Asian 3.8%; Americas 6.9%; Ashkenazi 3.9%; Finnish 5.0%; Middle Eastern 2.4%; Amish 2.3%.
Estimated TT genotype frequency.
Showing effects for C/C genotype
Neurology & Mental Health
Memory, Learning & Attention
Memory Performance. Evidence: 7/10. Source: PMID 28800603. Stronger Memory.
Neurodegenerative Diseases
Alzheimer's Disease. Evidence: 9/10. Source: PMID 22005930. Lower Risk.
Amyloid Deposition. Evidence: 4/10. Source: PMID 30361487. Lower Deposition.
Cardiovascular & Metabolic
Lipids & Cholesterol
Triglycerides. Evidence: 8/10. Source: PMID 26582766. Lower Levels.
Metabolic Syndrome & Insulin Resistance
Metabolic Syndrome. Evidence: 7/10. Source: PMID 22399527. Lower Risk.
Showing effects for C/T genotype
Memory Performance. Evidence: 7/10. Source: PMID 28800603. Typical Memory.
Alzheimer's Disease. Evidence: 9/10. Source: PMID 22005930. Increased Risk.
Amyloid Deposition. Evidence: 4/10. Source: PMID 30361487. Slightly Higher.
Triglycerides. Evidence: 8/10. Source: PMID 26582766. Slightly Higher.
Metabolic Syndrome. Evidence: 7/10. Source: PMID 22399527. Slightly Higher Risk.
Showing effects for T/T genotype
Memory Performance. Evidence: 7/10. Source: PMID 28800603. Weaker Memory.
Alzheimer's Disease. Evidence: 9/10. Source: PMID 22005930. Higher Risk.
Amyloid Deposition. Evidence: 4/10. Source: PMID 30361487. Higher Deposition.
Triglycerides. Evidence: 8/10. Source: PMID 26582766. Higher Levels.
Metabolic Syndrome. Evidence: 7/10. Source: PMID 22399527. Higher Risk.
What this genotype means for the people who carry it
Sample genotype: CC (Homozygous)
Double copies of the C allele are associated with stronger verbal memory performance during aging [1]. Clinical studies of postmenopausal women show that this genotype is linked to a lower risk of developing probable dementia compared to carriers of the T allele [2]. Brain imaging research indicates that individuals with this profile exhibit a slower rate of hippocampal atrophy, preserving critical brain structures involved in memory formation [3]. Furthermore, this genotype is associated with lower levels of cerebral amyloid deposition, a key pathological hallmark of Alzheimer's disease [4]. On a metabolic level, this genetic makeup is linked to lower circulating triglyceride levels and a reduced risk of metabolic syndrome [5]. These findings suggest that the C/C genotype provides relative protection against both cognitive decline and metabolic dysfunction.
Stronger verbal memory performance; Lower risk of late-life dementia; Typical brain structure preservation.
Sample genotype: CT (Heterozygous)
A single copy of the T allele is associated with a gradual decline in verbal learning and memory performance after age 60 [1]. Large-scale genetic studies indicate that this variant increases susceptibility to late-onset Alzheimer's disease [2]. Neuroimaging data show that carriers of this allele tend to have a faster rate of hippocampal atrophy and greater cerebral amyloid plaque deposition. This genetic variation also influences systemic lipid levels, predisposing individuals to higher circulating triglycerides [3]. Additionally, the presence of the T allele is linked to an elevated risk of developing metabolic syndrome [4]. These combined neurological and metabolic factors suggest that having one T allele moderately accelerates cognitive and metabolic aging processes.
Moderate risk of age-related memory decline; Slightly elevated risk of Alzheimer's disease; Slightly higher triglyceride levels.
Sample genotype: TT (Homozygous)
Two copies of the T allele are strongly linked to weaker verbal memory performance and accelerated cognitive decline in older age [1]. Research in older cohorts demonstrates that this genotype significantly elevates the risk of developing dementia and Alzheimer's disease [2]. Brain scans reveal that individuals with this profile experience a faster rate of hippocampal atrophy and increased accumulation of amyloid-beta plaques. This genotype is also associated with higher levels of total tau and altered tau-to-amyloid ratios in cerebrospinal fluid, indicating active neurodegeneration [3]. On the metabolic side, the T/T genotype is associated with higher circulating triglycerides and an increased susceptibility to metabolic syndrome. These findings highlight a pronounced genetic link to both cognitive vulnerability and lipid imbalances.
Weaker verbal memory performance in older age; Elevated risk of late-onset Alzheimer's disease; Higher circulating triglyceride levels.
Variants with shared genetic architecture
rs157580 · TOMM40 Gene · Chr 19 · Alzheimer's Disease Risk
rs2075650 · TOMM40 Gene · Chr 19 · Alzheimer's Disease Risk
rs1160985 · TOMM40 Gene · Chr 19 · Alzheimer's Disease Risk
Genome-wide association study of hippocampal atrophy rate in non-demented elders.
A Genome-Wide Association Study of Metabolic Syndrome in the Taiwanese Population.
Genome-wide association and interaction studies of CSF T-tau/Aβ42 ratio in ADNI cohort.
Content updated August 2026.
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