Alzheimer’s quietly ravages the brain long before symptoms appear, and now scientists have new clues about the dominolike sequence of those changes — a potential window to one day intervene.

Over the course of 20 years, a comprehensive research project in China followed middle-aged and older individuals, utilizing frequent brain scans, spinal punctures, and other examinations.

According to researchers, individuals who later developed Alzheimer’s had elevated levels of a protein associated with the disease in their spinal fluid 18 years before diagnosis, compared to those who maintained cognitive health. The study also identified additional markers of potential trouble at various intervals.

The exact process of how Alzheimer’s develops is still unknown to scientists. One indicator in the early stages is the presence of a sticky protein called beta-amyloid, which accumulates over time and causes blockages in the brain. However, having amyloid alone is not sufficient to impair memory, as even healthy individuals can have a significant amount of plaque in their brains. Another contributing factor is an abnormal tau protein that causes the formation of tangles that can damage neurons.

The latest study, released in The New England Journal of Medicine, provides a chronological sequence for the accumulation of these irregularities.

According to Dr. Richard Mayeux, an Alzheimer’s specialist at Columbia University who was not a part of the research, the significance of the study is significant.

Having an understanding of the timing of these bodily processes is crucial for evaluating novel treatments and potentially preventing Alzheimer’s, according to an editorial written by the author.

The results do not currently have any practical significance.

First treatment

More than 6 million Americans, and millions more worldwide, have Alzheimer’s, the most common form of dementia. There’s no cure. But last year, a drug named Leqembi became the first to be approved, with clear evidence that it could slow the worsening of early Alzheimer’s — albeit for a few months.

The method involves removing a portion of the amyloid protein buildup. Studies are also being conducted to determine if treating high-risk individuals before symptoms arise can delay the onset of Alzheimer’s disease. Additionally, there are other medications in development that aim to target tau.

Monitoring undetected changes in the brain is crucial for this type of investigation. It is already understood that in uncommon, genetic variants of Alzheimer’s that affect younger individuals, a harmful type of amyloid begins to build up approximately twenty years before any symptoms appear. At a later stage, tau also becomes involved.

The latest discoveries reveal the sequence in which biomarkers change in older individuals with Alzheimer’s disease.

The Innovation Center for Neurological Disorders in Beijing conducted a study comparing 648 individuals who were later diagnosed with Alzheimer’s and an equal number of healthy individuals. The first indication of amyloid build-up, a marker for Alzheimer’s, was found 18 years or 14 years before diagnosis, depending on the type of test used.

Differences in tau were detected next, followed by a marker of trouble in how neurons communicate. A few years after that, differences in brain shrinkage and cognitive test scores between the two groups became apparent, the study found.

Claire Sexton, the senior director of scientific programs at the Alzheimer’s Association, stated that having a greater understanding of potential targets for treating Alzheimer’s and knowing when to address them will lead to more efficient development of therapies and preventative measures. She added that upcoming blood tests will also aid in tracking amyloid and tau, making the process easier.