The evidence to date makes it clear that Alzheimer's disease isn't a condition in which amyloid-β alone drives progression of neurodegeneration. There is significant synergy between the aggregation of amyloid-β and tau protein, and between portions of the surrounding biochemistry. It isn't the solid deposits of amyloid-β and hyperphosphorylated tau that are the direct cause of cell dysfunction and death, but rather complex interactions related to these aggregates. Various studies have provided evidence to suggest that amyloid-β spurs tau aggregation, as well as vice versa, and it may be the case that both are true. The work here adds to the evidence for neurodegeneration to start with amyloid-β accumulation, which increases the pace at which tau aggregation later takes place. When it comes to actual damage to the brain, both cause significant harms, however.
Years ago, researchers noted that people with Alzheimer's disease have high levels of tau in the cerebrospinal fluid, which surrounds their brain and spinal cord. Tau - in the tangled form or not - is normally kept inside cells, so the presence of the protein in extracellular fluid was surprising. As Alzheimer's disease causes widespread death of brain cells, researchers presumed the excess tau on the outside of cells was a byproduct of dying neurons releasing their proteins as they broke apart and perished. But it was also possible that neurons make and release more tau during the disease.
In order to find the source of the surplus tau, researchers decided to measure how tau was produced and cleared from human brain cells. The researchers applied a technique known as Stable Isotope Labeling Kinetics (SILK). The technique tracks how fast proteins are synthesized, released and cleared, and can measure production and clearance in models of neurons in the lab and also directly in people in the human central nervous system. Using SILK, the researchers found that tau proteins consistently appeared after a three-day delay in human neurons in a laboratory dish. The timing suggests that tau release is an active process, unrelated to dying neurons.
Further, by studying 24 people, some of whom exhibited amyloid plaques and mild Alzheimer's symptoms, they found a direct correlation between the amount of amyloid in a person's brain and the amount of tau produced in the brain. Whether a person has symptoms of Alzheimer's disease or not, if there are amyloid plaques, there is increased production of this soluble tau. The findings are a step toward understanding how the two key proteins in Alzheimer's disease - amyloid and tau - interact with each other. "We knew that people who had plaques typically had elevated levels of soluble tau. What we didn't know was why. This explains the why: The presence of amyloid increases the production of tau."