Alzheimer's genes: Are you at risk?

Several genes have been associated with Alzheimer's disease, but more research is needed.

By Mayo Clinic Staff

Certain genes make you more likely to develop Alzheimer's disease.

Genes control the function of every cell in your body. Some genes determine basic characteristics, such as the color of your eyes and hair. Other genes can make you more likely to develop certain diseases, including Alzheimer's disease.

Researchers have identified a number of genes associated with Alzheimer's disease. Some genes increase your likelihood of developing the disease (risk genes). Others guarantee that you will develop a disease (deterministic genes), though these are rare. However, genetic risk factors are just one of the factors involved in getting Alzheimer's disease.

Most common late-onset Alzheimer's gene

The most common type of Alzheimer's disease usually begins after age 65 (late-onset Alzheimer's disease). The most common gene associated with late-onset Alzheimer's disease is a risk gene called apolipoprotein E (APOE).

APOE has three common forms:

  • APOE e2 — the least common — appears to reduce the risk of Alzheimer's.
  • APOE e4 — a little more common — increases the risk of Alzheimer's.
  • APOE e3 — the most common — doesn't seem to affect the risk of Alzheimer's

Genes aren't the only factor

Because you inherit one APOE gene from your mother and another from your father, you have two copies of the APOE gene. Having at least one APOE e4 gene increases your risk of developing Alzheimer's disease. If you have two APOE e4 genes, your risk is even higher.

But not everyone who has one or even two APOE e4 genes develops Alzheimer's disease. And the disease occurs in many people who don't even have an APOE e4 gene, suggesting that the APOE e4 gene affects risk but is not a cause. Other genetic and environmental factors likely are involved in the development of Alzheimer's disease.

Other late-onset genes

As research on the genetics of Alzheimer's progresses, researchers are uncovering links between late-onset Alzheimer's and a number of other genes. Several examples include:

  • ABCA7. The exact role of ABCA7 isn't clear, but the gene seems to be linked to a greater risk of Alzheimer's disease. Researchers suspect it may have something to do with the gene's role in how the body uses cholesterol.
  • CLU. This gene helps regulate the clearance of amyloid-beta from the brain. Research supports the theory that an imbalance in the production and clearance of amyloid-beta is central to the development of Alzheimer's disease.
  • CR1. A deficiency of the protein this gene produces may contribute to chronic inflammation in the brain. Inflammation is another possible factor in the development of Alzheimer's disease.
  • PICALM. This gene is linked to the process by which brain nerve cells (neurons) communicate with each other. Smooth communication between neurons is important for proper neuron function and memory formation.
  • PLD3. Scientists don't know much about the role of PLD3 in the brain. But it's recently been linked to a significantly increased risk of Alzheimer's disease.
  • TREM2. This gene is involved in the regulation of the brain's response to inflammation. Rare variants in this gene are associated with an increased risk of Alzheimer's disease.
  • SORL1. Some variations of SORL1 on chromosome 11 appear to be associated with Alzheimer's disease.

Researchers are continuing to learn more about the basic mechanisms of Alzheimer's disease, which may potentially lead to new ways to treat and prevent the disease.

As with APOE, these genes are risk factors, not direct causes. In other words, having a variation of one of these genes may increase your risk of Alzheimer's. However, not everyone who has one will develop Alzheimer's disease.

Early-onset Alzheimer's

A very small percentage of people who develop Alzheimer's disease have the early-onset type. Signs and symptoms of this type usually appear between ages 30 and 60 years. This type of Alzheimer's disease is very strongly linked to your genes.

Scientists have identified three genes in which mutations cause early-onset Alzheimer's disease. If you inherit one of these mutated genes from either parent, you will probably have Alzheimer's symptoms before age 65. The genes involved are:

  • Amyloid precursor protein (APP)
  • Presenilin 1 (PSEN1)
  • Presenilin 2 (PSEN2)

Mutations of these genes cause the production of excessive amounts of a toxic protein fragment called amyloid-beta peptide. This peptide can build up in the brain to form clumps called amyloid plaques, which are characteristic of Alzheimer's disease. A buildup of toxic amyloid-beta peptide and amyloid plaques may lead to the death of nerve cells and the progressive signs and symptoms of this disorder.

As amyloid plaques collect in the brain, tau proteins malfunction and stick together to form neurofibrillary tangles. These tangles are associated with the abnormal brain functions seen in Alzheimer's disease.

However, some people who have early-onset Alzheimer's don't have mutations in these three genes. That suggests that some early-onset forms of Alzheimer's disease are linked to other genetic mutations or other factors that haven't been identified yet.

Genetic testing

Most experts don't recommend genetic testing for late-onset Alzheimer's. In some instances of early-onset Alzheimer's, however, genetic testing may be appropriate.

In the case of APOE, just because you have the e4 variety doesn't mean you'll get Alzheimer's. Although many people with APOE e4 develop Alzheimer's, many don't. Conversely, some people with no APOE e4 genes develop Alzheimer's.

Most clinicians discourage testing for the APOE genotype because the results are difficult to interpret. And doctors can generally diagnose Alzheimer's disease without the use of genetic testing.

Testing for the mutant genes that have been linked to early-onset Alzheimer's — APP, PSEN1 and PSEN2 — may provide more certain results if you're showing early symptoms or if you have a family history of early-onset disease. Genetic testing for early-onset Alzheimer's may also have implications for current and future therapeutic drug trials.

Before being tested, it's important to weigh the emotional consequences of having that information. The results may affect your eligibility for certain forms of insurance, such as disability, long-term care and life insurance.

Researchers and genes

Researchers suspect that many more genes that haven't been identified yet affect the risk of Alzheimer's disease. Such information may prove vital in the development of new ways to treat, or even prevent, Alzheimer's disease in the future.

The Alzheimer's Disease Genetics Study, sponsored by the National Institute on Aging, is examining genetic information from families that have at least two family members who have developed Alzheimer's after age 65. If your family is interested in participating in this study, visit the website for the National Cell Repository for Alzheimer's Disease.

A number of other studies are evaluating the genetics of people with Alzheimer's disease and their family members. To learn more about these studies, and whether or not they're recruiting volunteers, visit the National Institute on Aging's Alzheimer's Disease Education and Referral Center website, or ask your doctor what trials might be available.

April 19, 2019 See more In-depth

See also

  1. MIND diet may cut Alzheimer's risk
  2. Adult day service
  3. Alzheimer's sleep problems
  4. Alzheimer's: New treatments
  5. Helping an Alzheimer's caregiver
  6. Alzheimer's 101
  7. Alzheimer's and dementia care: 8 tips for doctor visits
  8. Alzheimer's and daily tasks
  9. Alzheimer's and dementia: Tips for daily care
  10. Understanding the difference between dementia types
  11. Alzheimer's: Can a head injury increase my risk?
  12. Mediterranean diet
  13. Alzheimer's disease
  14. Alzheimer's disease: Can exercise prevent memory loss?
  15. Alzheimer's drugs
  16. Alzheimer's nose spray: New Alzheimer's treatment?
  17. Alzheimer's or depression: Could it be both?
  18. Alzheimer's prevention: Does it exist?
  19. Alzheimer's stages
  20. Alzheimer's test: Detection at the earliest stages
  21. Alzheimer's and holidays
  22. Antidepressant withdrawal: Is there such a thing?
  23. Antidepressants and alcohol: What's the concern?
  24. Antidepressants and weight gain: What causes it?
  25. Antidepressants: Can they stop working?
  26. Antidepressants: Side effects
  27. Antidepressants: Selecting one that's right for you
  28. Antidepressants: Which cause the fewest sexual side effects?
  29. Anxiety disorders
  30. Atypical antidepressants
  31. Axona: Medical food to treat Alzheimer's
  32. Benefits of being bilingual
  33. Caffeine and depression: Is there a link?
  34. The role of diet and exercise in preventing Alzheimer's disease
  35. Can music help someone with Alzheimer's?
  36. Can yoga help me keep caregiver stress in check?
  37. Caregiver stress
  38. Dementia caregiving: Dealing with the strain on your marriage
  39. Long-distance caregiving
  40. Clinical depression: What does that mean?
  41. CT scan
  42. CT scans: Are they safe?
  43. Depression and anxiety: Can I have both?
  44. Depression, anxiety and exercise
  45. Depression: Diagnosis is key
  46. Depression in women: Understanding the gender gap
  47. Depression (major depressive disorder)
  48. Depression: Provide support, encouragement
  49. Depression: Supporting a family member or friend
  50. Diabetes and Alzheimer's
  51. Diagnosing Alzheimer's
  52. Does obstructive sleep apnea increase my risk for Alzheimer's disease?
  53. Alzheimer's elder care
  54. Fish oil and depression
  55. Folic acid supplements: Can they slow cognitive decline?
  56. Ginkgo biloba: Can it prevent memory loss?
  57. Home safety tips for Alzheimer's caregivers
  58. How can I cope with caregiver guilt?
  59. Huperzine A: Can it treat Alzheimer's?
  60. Improve brain health with the MIND diet
  61. Intermittent fasting
  62. Is the definition of Alzheimer's disease changing?
  63. Depression and diet
  64. Lexapro side effects: Is breast tenderness common?
  65. Male depression: Understanding the issues
  66. MAOIs and diet: Is it necessary to restrict tyramine?
  67. Marijuana and depression
  68. Mayo Clinic Minute: 3 tips to reduce your risk of Alzheimer's disease
  69. Mayo Clinic Minute: Alzheimer's disease risk and lifestyle
  70. Mayo Clinic Minute New definition of Alzheimer's changes
  71. Mayo Clinic Minute: Women and Alzheimer's Disease
  72. Mediterranean diet recipes
  73. Memory loss: When to seek help
  74. Mild depression: Are antidepressants effective?
  75. Monoamine oxidase inhibitors (MAOIs)
  76. MRI
  77. Natural remedies for depression: Are they effective?
  78. Nervous breakdown: What does it mean?
  79. New Alzheimers Research
  80. Pain and depression: Is there a link?
  81. Pet therapy
  82. Phantosmia: What causes olfactory hallucinations?
  83. Phosphatidylserine supplements: Can they improve memory?
  84. Positron emission tomography scan
  85. Rapidly progressing Alzheimer's: Something else?
  86. Seeing Inside the Heart with MRI
  87. Selective serotonin reuptake inhibitors (SSRIs)
  88. Serotonin and norepinephrine reuptake inhibitors (SNRIs)
  89. Sharing Alzheimer's diagnosis
  90. Brain anatomy
  91. Sundowning: Late-day confusion
  92. Treatment-resistant depression
  93. Tricyclic antidepressants and tetracyclic antidepressants
  94. Video: Alzheimer's drug shows early promise
  95. MRI
  96. Vitamin B-12 and depression
  97. Vitamin B-12 and Alzheimer's
  98. Vitamin D: Can it prevent Alzheimer's & dementia?
  99. Young-onset Alzheimer's