Scientists Propose New Alzheimer's Definition Based On Biology

With this new construct, researchers can study Alzheimer’s from its earliest biological underpinnings to outward signs of memory loss and other clinical symptoms. (Photo: Pixabay)

Researchers have proposed a radical change in the way Alzheimer’s disease is defined, focusing on biological changes in the body, rather than clinical symptoms such as memory loss and cognitive decline. 

This proposed “biological construct” is based on measurable changes in the brain and is expected to facilitate better understanding of the disease process and the sequence of events that lead to cognitive impairment and dementia. 

With this new construct, researchers can study Alzheimer’s from its earliest biological underpinnings to outward signs of memory loss and other clinical symptoms, which could result in a more precise and faster approach to testing drug and other interventions. 

“Much of the general public views the terms dementia and Alzheimer’s disease as interchangeable, but they are not,” said Dr. Clifford Jack of the Mayo Clinic, who helped craft the guidelines published in the journal Alzheimer’s & Dementia: The Journal of the Alzheimer’s Association. 

 

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The proposed changes follow guidance announced earlier this year by the European Medicines Agency and the U.S. Food and Drug Administration to encourage the testing of new Alzheimer’s medicines based on biomarkers, rather than clinical symptoms.  

The moves would allow companies to test drugs in people before symptoms appear, offering a better chance of intervening before the disease has destroyed too many brain cells.

Under the proposed research framework, Alzheimer’s would be characterised by three general groups of biomarkers:  

  1. Beta-amyloid
  2. Tau and neurodegeneration
  3. Neuronal injury 

And leaves room for other and future biomarkers. Beta-amyloid is a naturally occurring protein that clumps to form plaques in the brain. Tau, another protein, accumulates abnormally forming neurofibrillary tangles which block communication between neurons. Neurodegeneration or neuronal injury may result from many causes, such as ageing or trauma, and not necessarily Alzheimer’s disease.

The purpose is that the new definition will help researchers pick better subjects on which to test new Alzheimer’s treatments, in which could help improve drug companies’ search for treatments. 

Experimental drugs in Alzheimer’s have so far had a poor track record, with hundreds of failures, including most recently a treatment from Merck, while Pfizer said in January it was quitting the field. 

One of the hallmarks of Alzheimer’s disease is the accumulation of amyloid-beta plaques in the patient’s brain, which is what most of these drugs have been focusing on. But according to recent imaging studies, report Reuters, 30% of people who have taken part in clinical trials for Alzheimer’s drugs didn’t have beta-amyloid in their brains. 

It will be exciting to see what scientists can make out of this new framework, as it put’s Alzheimer’s research more in line with other diseases.