VAI Voice

The official blog of Van Andel Institute
12 Jun 2019

Disease profile: Alzheimer’s disease

Alzheimer’s disease is the most common neurodegenerative disorder in the world and a leading cause of death among older Americans. Globally, an estimated 44 million people have Alzheimer’s.

It is marked by progressive loss of memory and cognitive abilities such as thinking, reasoning or performing simple tasks. Evidence suggests that the earliest stages of Alzheimer’s may start a decade or earlier before symptoms begin. Although a person may not show outward signs during this time, changes in the brain — namely the tangling of proteins called tau and the buildup of amyloid plaques — are occurring and causing the damage that leads to symptoms.

Risk factors

There is likely no one single cause of Alzheimer’s disease. Instead, it is believed to result from a complex mix of factors including:

  • Age: Age is the most important risk factor for Alzheimer’s disease, and may be related to the breakdown of normal processes required to keep brain cells healthy. 10 percent of people age 65 and older have Alzheimer’s.
  • Genetics: Genetic variants are important risk factors for Alzheimer’s. One prominent idea is called the amyloid cascade hypothesis, which suggests that mutations in three genes — APPPSEN1 andPSEN2 — lead to the buildup of beta-amyloid, exceptionally “sticky” protein fragments that eventually form plaques. As these plaques accumulate, they begin to interfere with communication between cells, which inappropriately may activate the immune system. This then leads to chronic inflammation, which damages and kills brain cells, triggering the disease’s symptoms.

There are other important genes as well, including:

    • APOE: Having certain types of the APOEgene can increase a person’s risk of developing Alzheimer’s.
    • TREM2TREM2has recently been found to cause a similar type of dementia to Alzheimer’s and is being investigated as a genetic risk for Alzheimer’s disease. It is the most significant genetic risk factor identified since the discovery of APOE.
  • Family history: People who have a close family member, such as a parent or sibling, with Alzheimer’s have a higher risk of developing the disease. This may be due to genetic factors, which can run in families, or shared exposure to certain environmental factors.
  • Lifestyle: Maintaining a healthy diet, getting adequate exercise, staying mentally and socially active and limiting smoking and alcohol consumption are important parts of overall healthy aging and may reduce the risk of Alzheimer’s.

How can research help?

Our understanding of Alzheimer’s has come a long way but there still is much more to uncover. Figuring out how and why Alzheimer’s occurs and progresses — and why and how it varies from person to person — will help scientists develop new strategies to detect it early and potentially slow or stop disease progression.

At the Institute, this work includes:

  • Decoding the genetic variants that impact Alzheimer’s disease risk
  • Sleuthing out the epigenetic changes that may propel disease progression
  • Understanding the broader landscape of dementia and other Alzheimer’s-related diseases

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