Time progression of Alzheimer’s disease studied

Cambridge University identifies possible cause of disease progression

For the first time, scientists:inside have been able to determine the speed of the different processes that trigger Alzheimer’s by analysing human data. They found that the disease may progress differently than previously thought, which could have important implications for the development of potential therapies.

An international team of researchers, led by the University of Cambridge, discovered that Alzheimer’s does not start from a single point in the brain and then cause a chain reaction that leads to the death of brain cells. Instead, the disease reaches different regions of the brain early on. The speed at which Alzheimer’s kills cells in these regions by forming toxic protein accumulations determines the overall progression of the disease.

The researchers studied post-mortem brain samples from Alzheimer’s patients and PET scans from living patients at different stages of the disease to track the accumulation of tau, one of the two main proteins associated with Alzheimer’s disease.

In Alzheimer’s, tau and another protein, amyloid-beta, form into bundles and plaques called aggregates. This leads to memory loss, personality changes and difficulty in performing everyday tasks.

Not spread, but proliferation of aggregates decisive

The researchers combined five different data sets and applied them to a unified mathematical model. They found that the mechanism controlling the progression of Alzheimer’s is the proliferation of aggregates in individual brain regions, rather than the spread from one region to another.

These findings, published in the journal Science Advances, open new avenues for understanding the progression of Alzheimer’s and other neurodegenerative diseases, as well as new opportunities for developing future treatments.

For a long time, the processes in the brain that lead to Alzheimer’s disease have been described with terms such as “cascade” or “chain reaction”. The disease is difficult to study because it develops over decades and a definitive diagnosis can only be made after brain tissue samples are examined after death.

Important contribution to the development of new treatment strategies

Previous studies of the disease were mainly based on animal models. Results from mouse studies indicated that Alzheimer’s spreads rapidly when toxic protein accumulations colonise different parts of the brain.

The researchers have now found that the replication of tau aggregates is surprisingly slow and can take up to five years. The scientists believe that their method could contribute to the development of treatments for Alzheimer’s disease by targeting the key processes involved in the development of the disease in humans. The methodology could also be applied to other neurodegenerative diseases such as Parkinson’s.

The researchers now plan to investigate earlier processes in disease development and extend the studies to other diseases, such as frontotemporal dementia, traumatic brain injury and progressive supranuclear palsy, in which tau aggregates are also formed.

Dr Georg Meisl, from the Yusuf Hamied Department of Chemistry in Cambridge and lead author of the study, explained: “Until now, Alzheimer’s was thought to develop in a similar way to many cancers: The aggregates form in one region and then spread to the brain. Instead, we found that at the onset of Alzheimer’s, aggregates are already present in multiple regions of the brain, so trying to stop the spread between regions does little to slow the disease.”

Chemical kinetics makes studies on patients possible

Advances in chemical kinetics made at Cambridge over the past decade have now enabled researchers to model the processes of aggregation and spread in the brain. Advances in PET scanning and improvements in the sensitivity of other brain measurements have also contributed to research into the disease.

Professor Thomas Knowles of the Department of Chemistry and co-author of the study emphasised the importance of using human data rather than imperfect animal models: “Fifteen years ago, the basic molecular mechanisms were determined by us and others for simple systems in a test tube, but now we can study this process at the molecular level in real patients, which is an important step for developing therapies.”

Professor Sir David Klenerman of the UK Dementia Research Institute at the University of Cambridge, one of the study’s lead authors, stressed the need to be even more effective in helping neurons prevent aggregates from forming in order to develop an effective treatment.

The scientists hope that their focus on the key processes involved in the development of Alzheimer’s disease and the application of their methodology to other neurodegenerative diseases will help to improve understanding of these diseases and enable new therapeutic approaches. The current study marks a significant advance in Alzheimer’s research and opens doors for future investigations and potential treatments.


Georg Meisl et al; “In vivo rate-determining steps of tau seed accumulation in Alzheimer’s disease”; Science Advances; 2021