The Relationship Between Amyloid, Tau, and Cognition
A recent article published on ALZFORUM discussed research from the first longitudinal study that conducted repeated scans on older adults for both amyloid and tau over several years, and correlate those PET scan results with cognitive changes.
Scans were analyzed from 60 men and women that took part in the Harvard Aging Brain Study who were cognitively healthy and between the ages of 65 and 85 years of age. In addition to the scans, the participants completed cognitive testing each year to monitor cognitive changes. Participants were divided into groups of high and low amyloid as measured from the initial scan.
Over the years of the study, amyloid and tau levels rose in both of the groups and cognitive scores decreased. Those with the faster rate of tau accumulation had the fastest cognitive decline. On average, this entire process was sped up in the group with higher levels of amyloid in the brain initially.
Amyloid is deposited in the brain years before symptoms of Alzheimer’s disease begin to appear. This makes amyloid PET scans the most useful tool in detecting early pathology of the disease.
The study mentioned above shows that a reduction of tau may help to preserve cognition in those with high amyloid accumulation.
In brains without the presence of amyloid, the tau tangles stay confined to the medial temporal lobe as a part of normal aging. In brains where amyloid is present, the tau tangles invade the surrounding areas of the brain.
Studies support the theory that tau spreads through interconnected neurons, and that the spreading of tau depends of the presence of amyloid, as well as, the functional and structural connections between regions of the brain.
In addition to amyloid PET scans, tau PET scans are useful to track disease progression in clinical trials research. Currently, cognitive tests are helpful in tracking the progression, but take a long time to show any significant responses to clinical trials drugs.
Because amyloid may boost the accumulation of tau, people who accumulated amyloid at a fast rate throughout the study, experienced the most rapid increase of tau, and the largest cognitive decline.
Amyloid alone (without any presence of tau) has a weak affect on cognition, but as amyloid levels rise, it triggers a burst of tau production with ensuing cognition loss.
These findings help put the pieces in temportal order: amyloid, tau, and then cognitive decline. Tau PET biomarkers may get us closer to finding an effective disease modifying drug to combat Alzheimer’s disease. Larger studies will be needed to further evaluate this data and to fully understand the progression of this disease.