New research sheds light on neurodegenerative disease progression
In a breakthrough study led by Georg Meisl, scientists at the University of Cambridge found that targeting the local replication of harmful tau protein clusters in the brain could be a key component in finding more effective treatment methods for Alzheimer’s. In a The Daily Beast interview Tuomas Knowles (co-senior author of the study along with Dr. Meisl) states that “Alzheimer’s is a disease defined by misbehaving proteins.” This study may also provide insights into chronic traumatic encephalopathy (CTE), a neurodegenerative disease associated with repetitive concussions and head impacts.
The study investigates gaps between Alzheimer’s studies (typically focused on mice and tissue) and the progression of Alzheimer’s in humans. Focusing on the tau protein, researchers in this study created their own data from 25 human brain slices in combination with data from a total of 458 subjects from other studies, including mice and humans. Dr. Meisl’s team measured the rates of replication and tau levels in organisms and tissue in varying stages of dementia. Typically, the progression of Alzheimer’s has two components: 1) the physical spread of a harmful protein throughout the brain and 2) the local replication and multiplication of clusters of that protein.
A key finding in the study was that decreasing the local replication by a factor of three substantially slowed the progression of Alzheimer’s while reducing the physical spread of tau to additional brain regions by the same factor did not result in significant changes. This lack of impact may be because from Alzheimer’s stage three (out of six) onward, “local replication, rather than spreading between brain regions, is the main process controlling the overall rate of accumulation of tau in neocortical regions.” The study also found that tau replication doubles around every five years in humans, which is far slower than replication rates in mice and test-tube subjects.
These findings provide crucial information on the “rate-limiting” factor of Alzheimer’s as potentially being the local replication of protein clusters. If further research proves this correct, it could mean that slowing the local replication of tau clusters could slow the overall progression of the disease. This study highlights the potential next steps in combating other neurodegenerative diseases, such as CTE, because many are linked to the spread of tau and other harmful proteins that work in similar ways.