Scientists have recently discovered that Alzheimer’s disease silently attacks the brain long before any symptoms become noticeable. They have also uncovered new information about the sequential pattern of these changes, similar to a domino effect, which could potentially provide an opportunity for intervention in the future.

Over the course of 20 years, a comprehensive study in China monitored individuals between middle age and old age through frequent brain scans, spinal taps, and other examinations.

Researchers reported on Wednesday that individuals who later developed Alzheimer’s disease had elevated levels of a protein associated with the disease in their spinal fluid 18 years before diagnosis, in comparison to those who maintained cognitive health. The study also found evidence of another biomarker linked to potential Alzheimer’s risk every few years following the initial discovery.

Researchers are unsure of the exact process by which Alzheimer’s disease develops. One of the first indications is the presence of a sticky protein known as beta-amyloid, which gradually accumulates into plaques that obstruct brain function. However, the presence of amyloid alone does not necessarily lead to memory impairment, as many individuals with healthy brains also have a significant amount of plaque. Another contributing factor is an abnormal tau protein that forms tangles, which can ultimately damage neurons.

The recent 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 expert at Columbia University who was not part of the study, the significance of the research is extremely significant.

Understanding the specific timing of these physiological occurrences is crucial for exploring novel methods of treatment and potentially, the prevention of Alzheimer’s disease, according to a commentary accompanying the study.

The results do not currently have any practical significance.

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 approved with clear evidence that it could slow the worsening of early Alzheimer’s — albeit for a few months.

This method functions by removing some of the build-up of amyloid protein. Researchers are also studying its potential to potentially delay the onset of Alzheimer’s in individuals at high risk who receive treatment before symptoms manifest. Additionally, there are other medications currently in development that aim to target tau.

Monitoring subtle alterations in the brain is crucial in this type of investigation. It was previously established that in uncommon, hereditary variations of Alzheimer’s disease that affect individuals at a younger age, a harmful type of amyloid begins to accumulate around twenty years before any symptoms appear, and eventually tau takes over.

The recent discoveries demonstrate the sequence of biomarker changes associated with the more prevalent late-onset Alzheimer’s disease.

The Innovation Center for Neurological Disorders in Beijing conducted a study comparing 648 individuals who were later diagnosed with Alzheimer’s to an equal number of individuals who did not develop the disease. The results showed that the presence of amyloid, a protein associated with Alzheimer’s, could be detected 18 or 14 years before diagnosis, depending on the specific test used.

Tau differences were identified first, followed by an indication of neuronal communication difficulties. The study also revealed noticeable variations in brain shrinkage and cognitive test performance between the two groups a few years later.

Claire Sexton, the senior director of scientific programs at the Alzheimer’s Association, stated that having a deeper understanding of potential treatment targets for Alzheimer’s and the appropriate timing for addressing them will greatly aid in the development of effective therapies and preventative measures. She also mentioned that blood tests, which are expected to be available soon, will play a key role in facilitating this process by simplifying the tracking of amyloid and tau.

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