Biomarkers are quantifiable indicators of illnesses (such as levels of certain proteins in blood) that may otherwise be difficult to diagnose. Researchers are actively searching for biomarkers for Alzheimer’s disease (AD). Current approaches focus on designating people as “positive” or “negative” for AD based on the amount of two proteins, amyloid-beta (Aβ) and phosphorylated tau (p-tau), in their brains. Patients with more Aβ and p-tau than a certain threshold are considered positive, indicating that they are likely to develop AD.

But more and more, clinicians are discovering exceptions to this yes/no designation system. For example, there have been many cases of those with significant Aβ plaque formation who remain “cognitively intact”, meaning they don't develop dementia or other symptoms of AD, throughout their lives. These exceptions highlight a disconnect between the total accumulation of these biomarkers and the impact on cognitioon. 

Scientists have challenged this static system in a new paper, published in a specialized journal for AD research, by introducing time-inclusive categories. Instead of focusing on protein levels, they categorized individuals by how rapidly their brains accumulated Aβ and p-tau. To demonstrate the utility of their system, the researchers analyzed a group of 250+ cognitively normal individuals to see if they could identify the Aβ and p-tau biomarker accumulation rate and their association with AD risk factors, like the APOE4 allele. Their system successfully separated volunteers into distinct groups for both biomarkers. They could also identify timepoints of “escalating accumulation” within each group. 

This system provides greater context for at-risk individuals and opens the door for earlier treatment of AD in people who were not considered positive for AD under previously used biomarkers. As more research points to the spread of the “amyloid burden” much earlier in life than the onset of cognitive decline, this new categorization can create more realistic diagnosis timelines for the currently incurable disease. To draw their final conclusions on the efficacy of their system, these researchers must continue monitoring study participants to determine when and if they develop AD. In its current state, their system is an untested theory beholden to the same master as those potentially afflicted with AD: time.