Frequently Asked Questions

Causes and Risk

What Causes Alzheimer’s Disease or Contributes to the Risk of Getting It?

Alzheimer’s disease is defined by abnormal clumps of protein deposits in the brain called amyloid plaques and tangled bundles of fibers in the brain called neurofibrillary or “tau” tangles. These are complex changes in the brain that begin long before symptoms appear. But why do plaques and tangles develop? We don’t yet know, but scientists suspect that several factors could play a role, although the significance of any particular risk factor appears to vary significantly from person to person. Factors associated with Alzheimer’s risk include:

Age. Alzheimer’s disease is not a “normal” part of the aging process; however, most people diagnosed with it are 65 years of age or older. About one in 13 people between 64 to 84, and about one in three people 85 and older, live with Alzheimer’s disease. And, although less common, Alzheimer’s symptoms can appear as early as the mid-40s (known as “early-onset Alzheimer’s disease”). Scientists do not yet know how age contributes to the damage to the brain that results in Alzheimer’s, but they are exploring a number of possibilities, including the shrinking of certain brain regions, inflammation, blood vessel damage, production of unstable molecules called free radicals, and mitochondrial dysfunction (a breakdown of energy production within a cell).

Genetics. “Genetic variants” are inherited permanent changes in one or more genes. Some genetic variants are strong predicters that a person will in fact develop a particular disease; others merely increase or decrease the risk of developing that disease. Researchers have found at least 75 genetic variants associated with Alzheimer’s risk. The vast majority of Alzheimer’s disease appears to develop as a result of multiple gene variants combined with other risk factors, and not by a single variant.

The apolipoprotein E (“APOE”) gene, which provides the blueprint for a protein that transports cholesterol in the bloodstream, is one of the genes associated with Alzheimer’s, but different forms (or “alleles”) of the gene impact the risk quite differently. For instance, the allele identified as APOEe2 is believed to provide some protection against Alzheimer’s and APOEe3 (the most common allele) is believed to have a neutral effect; but research indicates that an APOEe4 gene increases the risk of developing late-onset Alzheimer’s (and two copies of it create a higher risk than one) and, in some populations, is associated with early-onset Alzheimer’s. However, some people with the APOEe4 gene never develop Alzheimer’s, and genetic ancestry (i.e., the geographical region of biological descent) appears to affect the risk, as well.

Among the known genetic variants currently associated with Alzheimer’s, there are three extremely rare single gene variants believed to cause the disease: amyloid precursor protein (“APP”); presenilin1 (“PSEN1”); and presenilin2 (“PSEN2”). An estimated 1% or less of people living with Alzheimer’s are believed to carry these variants, but if a person inherits one of them, early-onset Alzheimer’s is a strong probability. And, people with Down syndrome are at higher risk than the general population because they have an extra copy of the chromosome (chromosome 21) that carries the APP gene.

Family History. Family history is not a definitive predicter. However, people with a first-degree relative (parent or sibling) who had or have the disease are at greater risk, and those with multiple first-degree relatives who had or have the disease are at even greater risk. When a disease runs in a family, both heredity and non-genetic factors may play a role.

Traumatic Brain Injury. A history of concussions and other traumatic brain injuries may also increase the risk of an Alzheimer’s diagnosis.

Lifestyle and Environment. Some researchers suspect that Alzheimer’s risk may increase as a result of various lifestyle and environmental factors, such as unmanaged chronic health issues (including high blood pressure, obesity, and heart disease), hearing loss, depression, physical inactivity, lack of mental stimulation, unhealthy diet, alcohol misuse, smoking, poor sleep hygiene, social isolation, and exposure to pollutants and toxins. Studies also have shown a correlation between higher rates of dementia, on the one hand, and inadequate access to resources and other socioeconomic factors, on the other.