By: Yeeun Lee
Every 65 seconds, someone in the U.S. develops Alzheimer’s. As more people get the disease, its growing burden is concerning because there is no definitive way to establish whether someone will acquire it—and no way to cure it. Many think of Alzheimer’s in a symptomatic framework because of the lack of differentiation between Alzheimer’s disease and dementia. For example, The Alzheimer’s Association defines it as “a type of dementia that causes problems with memory, thinking and behavior,” making it difficult for people to carry out their daily tasks. This description is definitely accurate but fails to recognize that Alzheimer’s is a biological disease and thus should be defined in a biological framework.
Increasingly, research advancements are showing that two proteins, Aβ (amyloid beta) and tau, are directly related to Alzheimer’s disease. This, in turn, has pushed for changing the way in which Alzheimer’s is understood. The National Institutes of health (NIH) believes that a biological model provides a “common language” that can unify research projects that are studying different stages of the disease. It also believes that it can “facilitate [a] better understanding of the disease process” by shifting the perspective towards specific and measurable biomarkers.
I had the great privilege of interviewing Dr. Lary C. Walker, an Associate Professor of Neurology and a proponent of a standard model of Alzheimer’s disease – using Aβ (amyloid beta) and tau proteins. He took me through a brief history of Alzheimer’s research and gave me his insights on the current knowledge regarding the disease as well as future directions.
Dr. Walked noted that, historically, to know if someone had Alzheimer’s, there was only one way to find out: looking at the brain microscopically. Thus, it could only be known whether or not the person had the disease after they were dead. Due to technology, we now have different methods, such as injecting radioactive agents that bind to different Alzheimer’s related proteins in the brain or measuring Aβ or tau proteins in the cerebrospinal fluid. Both techniques are invasive, expensive, and the injection technique requires radiation exposure to individuals. For these reasons, research on alternative diagnostic methods – such as blood tests that look for biomarkers – is crucial.
Recently, two articles were published in Nature and Nature Medicine regarding novel ways to test for Alzheimer’s that could reveal whether or not someone will develop the disease years before they start to show any symptoms. They are both blood tests, however one measures Aβ (amyloid beta) while the other measures neurofilaments (NF). So what is the difference? As Dr. Walker explained to me, individuals with Alzheimer’s have abnormal levels of amyloid beta, which deposits in amyloid-β plaques in their brains. In the article describing high-performance plasma amyloid-β biomarkers, these proteins were shown to be accurately measured in the blood. This amyloid-β blood test is more specific when it comes to Alzheimer’s as it tests for the presence of a protein that is characteristic of Alzheimer’s disease.
The neurofilament blood test, on the other hand, is more general. As neurons die, they release neurofilaments, which progressively make their way into the blood and cerebrospinal fluid. And so, this test measures neurofilament levels and uses it as an early indicator of neurodegeneration. However, it is more generic as it only detects neuron death, which could be caused by something else, such as a head injury. Regardless, in the long and previously fruitless search for blood biomarkers of Alzheimer’s disease, these results are breakthroughs and proof of progress.
A critical question remains: would anyone want to know that they are going to be demented when there’s no cure? Ultimately, it is a personal decision and opinions vary greatly. Some people might want to know to have time to get prepared, while others would rather not know. However, in our technologically advanced era, genetic information is easily accessible through consumer products such as 23andMe. These kits inform individuals on information regarding their APOE4 allele, which is a gene variant that can increase an individual’s risk of acquiring Alzheimer’s disease. While there is still no cure, the discovery of these new tests for blood biomarkers is crucial and useful. These breakthroughs are essential for testing current and future clinical drugs and treatments, and so it is useful that people are more willing to participate in these new, less invasive diagnostic tests. The results of the identification of these biomarkers also supports the move towards a standard model of Alzheimer’s that is defined by its biology, rather than by its symptoms.
Undeniably, Alzheimer’s has devastating physical and social consequences. More and more, experts on the field such as Dr. Walker consider it of utmost importance to define Alzheimer’s by its biology. By defining it by its biomarkers, amyloid-β and tau, a clear distinction between Alzheimer’s disease and dementia due to other causes can be made. Dementia is an umbrella term used to describe a range of signs and symptoms such as memory loss, confusion, and behavior change. Aging, having a stroke or having a neurodegenerative disease like Huntington’s disease can all cause dementia. Alzheimer’s disease, however, is the most common cause of dementia, and for this reason better diagnostic tests are badly needed. Having a standard model that defines it as a biological disease will facilitate and advance research and hopefully get us closer to one day finding a cure.
 Walker et al., “A standard model of Alzheimer’s disease.” Prion (2018) 12:261-265. Epub 9 October 2018.
 Nakamura et al., “High performance plasma amyloid-β biomarkers for Alzheimer’s disease.” Nature (2018) 554:249-254. Epub 31 January 2018.
 Preische et al., “Serum neurofilament dynamics predicts neurodegeneration and clinical progression in presymptomatic Alzheimer’s disease.” Nature Medicine (2019) 25:277-283. Epub 21 January 2019.