Alzheimer's Causes

Written by Wendy Leonard, MPH | Published on August 8, 2014
Medically Reviewed by George Krucik, MD, MBA on August 8, 2014

Alzheimer's Disease Causes

While much progress has been made in Alzheimer’s disease (AD) research, the exact cause is unknown. Many scientists 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 involved with memory, including how immediate or short-term memories are stored into long-term memories.

Your ability to function in everyday life also can be affect 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, to recalling if you turned off the stove.

The hippocampus also is essential to both 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 AD sufferers 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. It acts like railroad tracks, and safely guides and transports nutrients, molecules, and information to other cells. An important fiber-like protein called tau is responsible for keeping those microtubules stable. 

The tau’s chemical make-up 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 Alzheimer’s Disease

Researchers are certain of a genetic component to 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.

But 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,  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. And scientists have long believed amyloid plaques — and more specifically their building up to toxic levels — 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)
  • PSEN-1 (on chromosome 14)
  • PSEN-2 (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. They are believed to help produce amyloid protein, which forms amyloid plaques and are the hallmarks of AD. 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, and/or grandparent) suffered from the condition.

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