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Causes of Alzheimer’s Disease

Alzheimer’s disease overview

Fast facts

  1. The exact causes of Alzheimer’s disease are still unknown.
  2. Amyloid plaques, neurofibrillary tangles, and genetics are all thought to play a role in causing Alzheimer’s disease.
  3. Early-onset Alzheimer’s disease is caused by known genetic mutations and is not related to the more common age-associated Alzheimer’s.

Alzheimer’s disease (AD) is a neurodegenerative disease that causes brain cell death. This progressive disease, which causes a distinct pattern of pathological changes in the brain, is most common among older adults. However, it’s possible for adults as young as 30 to experience early-onset Alzheimer’s.

People who suffer from this condition may start off experiencing mild forgetfulness and confusion. As the disease progresses and brain cells die, symptoms become more apparent. Someone with AD may become lost in familiar places and forget conversations. The disease can also affect thinking, reasoning, and decision-making, and cause mood and behavioral changes.

While much progress has been made in AD research, the exact cause is unknown. Although scientists don’t fully understand the triggers, factors that may contribute to the disease include genetics and lifestyle and environmental factors. Many scientists also believe that a buildup of two abnormal structures in the brain play an important role. These structures are called amyloid plaques and neurofibrillary tangles.

Amyloid plaques

Amyloid plaques are dense, mostly insoluble clumps of protein fragments. They leave a highly damaging substance outside and around the brain’s nerve cells.

People with AD have a buildup of these plaques in their hippocampus. The hippocampus is the part of your brain involved with memory, including how short-term memories are stored into long-term memories.

Your ability to function in everyday life can be affected by an unhealthy hippocampus. Everything you do involves your ability to acquire, store, and retrieve memories. This can be anything from remembering if you ate lunch, to recognizing a loved one or recalling if you turned off the stove.

The hippocampus is also essential to spatial memory and spatial navigation. Spatial memory is how you retain information about your surroundings. Spatial navigation involves how you travel to a destination. Research suggests early hippocampus damage may explain why people with AD often wander and get lost.

Neurofibrillary tangles

Neurofibrillary tangles are insoluble, twisted fibers that clog the brain from the inside out.

Brain nerve cells (called neurons) have a special transport system called microtubules. They act like railroad tracks and safely guide and transport nutrients, molecules, and information to other cells. An important fiber-like protein called tau is responsible for keeping those microtubules stable.

The chemical make-up of tau proteins is altered in people with AD. The threads of tau become tangled and twisted. Thus, the microtubules become unstable and disintegrate, which collapses the entire neuron transport system.

This series of events may be related to the first visible sign of AD: memory loss. More research is needed to determine if amyloid plaques, tangles, and tau are a direct cause of AD.

Genetics of AD

Researchers believe genetics play a role in whether you develop AD. In the elderly, the gene most associated with the onset of symptoms is located on chromosome 19. It’s called apolipoprotein E (APOE).

There are several versions (alleles) of APOE. According to the National Institute on Aging, about 40 percent of people who develop AD later in life have an APOE e4 allele. A blood test can determine if you have it.

That said, it’s still not possible to predict who will develop AD. Some people with one or even two APOE e4 alleles never develop the disease. Others who get AD don’t have any APOE e4 alleles. Still, having an “AD gene” does increase your risk.

One of these newly identified genes that increase your risk is CD33. It causes the body to not eliminate as many amyloid plaques as it should. Scientists have long believed that the buildup of amyloid plaques likely plays a key role in degradation of brain neurons.

Genetics of early-onset AD

Genetic studies of families with a history of early-onset AD have identified mutations in three different genes.

  • APP (on chromosome 21)
  • PSEN1 (on chromosome 14)
  • PSEN2 (on chromosome 1)

These genes are thought to be responsible for the rare form of AD that afflicts men and women in their early 30s or 40s. These mutations are believed to help produce amyloid protein, which forms amyloid plaques. These mutated genes do not play a role in the more common late-onset AD.

Approximately 50 percent of people who have a parent with early-onset AD will likely inherit the genetic mutation and develop the disease. For those young individuals where neither parent had early-onset AD, research has found that often a second-degree relative (e.g., an uncle, aunt, or grandparent) suffered from the condition.

Outlook for AD

Although there’s no cure for AD, treatment can improve cognitive and behavioral symptoms. There’s no definitive way to prevent AD, but maintaining a healthy lifestyle may reduce your risk. This includes:

  • eating a healthy diet
  • losing excess weight
  • quitting smoking
  • getting regular physical activity (150 minutes per week)
  • adding foods with omega-3 fats, such as salmon, to your diet or taking fish oil supplements
  • getting plenty of sleep
  • being socially active

Brain puzzles and other mental exercises can also improve cognitive function and lower your risk.

Q&A

You asked, we answered

  • Is there anything I can do to prevent developing amyloid plaques and neurofibrillary tangles?
  • Thus far, scientists are not certain if the deposition of amyloid plaques and neurofibrillary tangles come from the disease or are the cause of the disease. The best advice to offer is to maintain good overall health. This includes eating well and exercising. Some research suggests that being cognitively active by engaging in mentally stimulating activities may also help.

    - Timothy J. Legg, PhD, CRNP
  • Answers represent the opinions of our medical experts. All content is strictly informational and should not be considered medical advice.

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