Alzheimer’s Disease Begins Much Sooner Than Symptoms, Scientists Suggest

Billion Photos/Shutterstock

Alzheimer’s disease is a devastating malady of the mind – a disorder that attacks the patient’s identity, erases their memories, and fundamentally changes who they are. For this reason, researchers looked at a decade’s worth of data to see if they could find the earliest precursor to the disease.

“The reason many promising drug treatments have failed to date is because they intervened at the end-stage of the disease when it’s too late,” said senior author Paul Aisen in a statement. “The time to intervene is when the brain is still functioning well – when people are asymptomatic.”


The study, published in The Journal of the American Medical Association, investigated data from the Alzheimer’s Disease Neuroimaging Initiative.

They measured the level of amyloid plaque – clusters of sticky, toxic proteins that accumulate in the brain and leave a jumble of dead, snarled neurons – in 445 cognitively normal people for up to 10 years to see whether any changes occurred. During the initial assessment, 242 subjects had normal amyloid levels and 202 had elevated levels.

After four years, 32 percent of the elevated-amyloid individuals had developed symptoms of early stage Alzheimer’s disease, compared to only 15 percent of normal-amyloid participants.

After 10 years and with a smaller sample size, 88 percent of people with elevated amyloid showed a significant decline on cognitive tests, compared to only 29 percent of people with normal amyloid.


The elevated group was also older, less educated, and many carried at least one copy of the ApoE4 gene – a genetic risk factor that increases the odds a person will develop the disease.

This means the destruction wrought by Alzheimer’s disease likely begins years before deterioration and symptoms are detected. The results suggest the incubation period for elevated amyloid plaque occurs at the asymptomatic stage and can last longer than the dementia itself.

Although the study reiterates some known facts about the disease, it’s important to confirm what scientists thought: Brain-clogging plaque in the brain is the first warning sign during the earliest stage of Alzheimer’s disease.

To illustrate the need for early intervention, the team liken amyloid plaque in the brain to cholesterol in the blood. They are both red flags before devastation hits. 


“We’ve learned that intervening before the heart attack is a much more powerful approach to treating the problem,” said lead author Michael Donohue. The same, they believe, holds true for Alzheimer’s disease. 

They hope that finding a way to remove amyloid at the preclinical stage will stop the deterioration of Alzheimer’s in its tracks. 

“To have the greatest impact on the disease, we need to intervene against amyloid, the basic molecular cause, as early as possible,” said Aisen. “This study is a significant step toward the idea that elevated amyloid levels are an early stage of Alzheimer’s, an appropriate stage for anti-amyloid therapy.”

A representation of amyloid plaques in the brain due to Alzheimer's disease. Juan Gaertner/Shutterstock


  • tag
  • early-stage,

  • neurodegeneration,

  • Alzheimer's disease,

  • amyloid plaque,

  • protein buildup,

  • precurser,

  • preclinical