Potential Causes of Late-Onset Alzheimer’s
It is very likely that a combination of genetic, lifestyle, and environmental factors contribute to the risk of developing this form of Alzheimer’s disease (AD), which occurs after age 60. The exact causes are not yet known.
- GeneticsThere is no single gene mutation that consistently causes late-onset Alzheimer’s. Instead, the late-onset form seems to represent the combined effect of multiple genes, each of which increases the risk a little. The best known of these is the apolipoprotein E gene (ApoE).
- LifestyleResearchers are actively exploring how diet, exercise, the management of medical conditions such as diabetes or high blood pressure, and other lifestyle factors contribute to the risk of developing AD.
- EnvironmentEducation level, head injuries, and other environmental influences may also play a role in AD, and scientists are exploring these avenues.
Causes of Familial (Early-Onset) Alzheimer’s
Specific genetic mutations are usually associated with the development of the familial (early-onset) form of the disease. Familial Alzheimer’s disease (FAD) is a rare form of the illness, affecting fewer than five percent of Alzheimer’s patients. All FAD is early-onset, meaning the disease develops before age 60. FAD results from mutations in one or more of at least three genes. If even one of these mutated genes is inherited from a parent, an individual will almost always develop early-onset Alzheimer’s disease.
A Gene That Can Affect Alzheimer’s Risk
Scientists have identified more than 20 genes that appear to influence the development of Alzheimer’s disease.
With one exception, these genes are not considered to be significant risk factors, either because they are rare or because their effect is too limited.
The gene that matters most is apolipoprotein E (APOE). There are three different APOE forms, called variants:
- e2 is an uncommon, protective form of the gene.
- e3, the most prevalent form, is believed to neither decrease nor increase risk.
- e4 raises Alzheimer’s risk and also makes it more likely the disease will develop at an earlier age.
A meta-analysis of 20 studies, cited by the Alzheimer’s Association, discovered that 56 percent of Americans diagnosed with Alzheimer’s had one copy of the e4 gene; 11 percent had two.
Other risk factors for Alzheimer’s include vascular problems — those related to blood vessels in the brain.
Damaged arteries harm the brain by interfering with the flow of blood, depriving brain cells of oxygen and essential nutrients like glucose; preventing the elimination of toxic beta-amyloid and tau proteins; and leading to damaging inflammation.
Alzheimer’s disease seems to be both a cause and a consequence of these vascular issues.
Researchers are working to identify exactly how and why this happens with the goal of interfering with this cycle.
A 2017 study in JAMA, following 322 subjects for over 20 years, found a relationship between vascular risk factors in middle age — obesity, smoking, high blood pressure, diabetes, and high cholesterol — and amyloid plaques in the brain.
The researchers found that subjects who had one risk factor had an 88 percent increased risk for elevated levels of amyloid plaques. People with two or more risk factors had almost triple the risk.