Causes of Alzheimer’s Disease

Alzheimer’s disease is a progressive neurodegenerative disorder that is characterized by declining mental abilities that affect memory, cognitive function, and personality. It is the most common cause of dementia.

While its exact cause remains unknown, many risk factors contribute to the likelihood of developing the disorder.

Plaques and tangles

Whatever the original trigger(s) may have been, the symptoms of Alzheimer’s develop because of beta-amyloid plaques and tau tangles — clumps of two proteins that accumulate to toxic degrees inside of brain nerve cells, or neurons.

Beta-amyloid is a fragment of a larger protein called amyloid precursor protein, or APP. While the exact function of APP remains unknown, it has been implicated in cell communication, nerve cell migration, and antimicrobial activity, among other possible functions.

For unclear reasons, the chemically “sticky” beta-amyloids sometimes clump together into plaques. As these plaques grow, they interfere with cell-to-cell communication and trigger an inflammatory immune response. Both of these actions result in the death of the affected nerve cells.

Tau is a protein that normally transports nutrients and other molecules into brain cells, and forms part of the cell’s internal support structure. In Alzheimer’s, tau twists into abnormal shapes, and these misfolded proteins link together into so-called “tau tangles.” The ensuing disruption to normal cellular transport contributes to brain cell death.

Genetics and family history

Genetics play a role in influencing one’s likelihood of developing Alzheimer’s, but there is as yet no known definitive genetic cause.

Alzheimer’s is broadly defined as either late-onset or early-onset, with each affected by different genetic components.

Late-onset Alzheimer’s, which tends to affect people from their mid-60s on, has no known specific genetic cause but does associate with a variant of the apolipoprotein E (APOE) gene as a possible risk factor. Although APOE is thought to increase a person’s risk of developing Alzheimer’s, inheriting it does not mean a person will develop the condition.

Accounting for fewer than 10% of all cases, early-onset Alzheimer’s tends to occur in individuals between their mid-30s and mid-60s. Some cases appear to stem from inherited changes in one of three genes: APPpresenilin 1 (PSEN1), and presenilin 2 (PSEN2). The abnormal proteins produced by mutations in these genes all affect the breakdown of the APP protein, which can lead to amyloid plaques.

Aging

Aging is the greatest risk factor involved in Alzheimer’s, as cases generally develop later in life.

Many biological systems grow less efficient as people age, which affects an individual’s risk of developing various conditions, including Alzheimer’s. Parts of the brain shrink and inefficiencies in cellular energy production lead to the production of free radicals, while inflammation becomes more common, and blood vessels accumulate damage.

It is important to note, however, that although these things happen with age, they do not imply a certainty of growing ill because of them. Clinicians note that many people live into old age without developing dementia.

Environmental factors

Various studies have found associations between air pollution and Alzheimer’s. Tiny particles of pollutants found in the air can enter the brain and studies in mice suggest that might cause biological changes. Epidemiological studies also have found the incidence of Alzheimer’s and other dementias to rise in areas of greater pollution.

To date, however, a direct link between air pollution and Alzheimer’s remains elusive.

Lifestyle factors

Certain lifestyle choices are linked to varying risks for Alzheimer’s and related dementias. These include smoking, alcohol consumption, exercise, diet, sleep patterns, and social engagement.

Several lifestyle risk factors relate to heart health and form the basis for the hypothesis for a heart-head connection in the development of dementias. Lifestyle features related to this include smoking, exercise, and diet, all of which affect vascular and cardiac health.

Smoking is a known risk factor for developing dementia, although the exact reasons remain unknown and may be varied. Smoking leads to vascular problems that are themselves known dementia risk factors, such as stroke and brain bleeds. Additionally, the toxins found in cigarette smoke increase oxidative stress — an imbalance between the production of free radicals and the ability of cells to detoxify them — and inflammation.

Numerous studies have found that physical exercise plays a large role in healthy aging and is linked to better performance regarding working memory and cognitive flexibility.

Heart-healthy diets, such as the Mediterranean and DASH (dietary approaches to stop hypertension) appear to tie to better vascular and cognitive health. These diets generally feature poultry and seafood over red meat and are high in vegetables, fruits, and nuts; they encourage limited fat and sugar consumption.

Similar to the biological changes associated with smoking, alcohol causes changes in the brain. Alcohol use disorders associate with a higher risk of dementias, particularly of those with an earlier onset.

Social interactions — and generally engaging in mentally and socially stimulating activities — require and reinforce the sort of cognitive and memory-related skills that decay in Alzheimer’s, such as taking in and interpreting new information and adjusting one’s reactions to social cues. Staying socially engaged also boosts self-esteem, which contributes to things like better eating, exercise, and sleep habits, all of which also associate with lower dementia risk.

Related to finding ways to remain mentally stimulated, research has identified a connection between higher levels of education and a lower risk for Alzheimer’s and related dementias.

Metabolic factors

Certain metabolic disorders, including Cushing’s disease, porphyria, and type 2 diabetes, contribute to abnormal brain function. Left untreated, brain damage can become permanent, raising the risk of developing dementia.

Down syndrome

Related to genetic risk factors, people with Down syndrome have a partial third copy of chromosome 21 (usually there are two copies of each chromosome) and a higher risk for Alzheimer’s disease. Several genes on this chromosome have been identified as possibly contributing to this increased risk, although no direct link between any one of them has yet been proven.

 

Last updated: June 18, 2021

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Alzheimer’s News Today is strictly a news and information website about the disease. It does not provide medical advice, diagnosis or treatment. This content is not intended to be a substitute for professional medical advice, diagnosis, or treatment. Always seek the advice of your physician or other qualified health provider with any questions you may have regarding a medical condition. Never disregard professional medical advice or delay in seeking it because of something you have read on this website.

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