Alzheimer's-related protein forms rapidly in the brain

The researchers studied tau and beta-amyloid, two proteins central to Alzheimer's disease. Newly formed tau was detectable within hours, while deposits of beta-amyloid, known as amyloid plaques, showed far less turnover.

Tracking newly formed proteins

The study examined brain tissue samples from 18 patients with suspected normal pressure hydrocephalus (NPH), a condition sometimes called "water on the brain." The patients were scheduled for surgery to have a shunt implanted to drain excess fluid from the brain. During the procedures, researchers collected tissue samples roughly the size of a grain of rice.

Before surgery, some patients received leucine, an amino acid labeled with a stable isotope (¹³C₆-leucine). The labeled amino acid was incorporated into newly synthesized proteins, allowing the researchers to identify them using advanced imaging techniques and proteomics.

Amyloid plaques, a hallmark of Alzheimer's disease, were found in nine of the patients.

The international study was published in Nature Communications. Jörg Hanrieder, Professor at the Institute of Neuroscience and Physiology, Sahlgrenska Academy at the University of Gothenburg, is one of the senior authors.

“Much of what we know about Alzheimer's disease comes from examining the brain after death, when disease-related changes are already well established. This study brings us closer to investigating the disease in its earliest stages. It allows us to examine not only what changes occur, but also when they arise and how quickly they evolve,” he says.

New insights into tracking the disease

The researchers also compared brain tissue with cerebrospinal fluid samples. They found that the protein profile in fluid collected from the brain's ventricles closely resembled that of the brain tissue. Their analyses showed that newly formed tau could be detected after approximately three hours and that the protein had an estimated half-life of around 34 days.

The team also found that phosphorylated tau217 (p-tau217), an established blood biomarker for Alzheimer's disease, accumulated in and around amyloid plaques. The finding offers new insights into the relationship between the two proteins.

“Understanding how amyloid and tau behave differently could help us determine when to assess whether a treatment is affecting the disease and when those changes should become detectable in blood or cerebrospinal fluid,” says Jörg Hanrieder.

The findings could help researchers design future treatment studies, particularly those aimed at detecting early signs of treatment effects. However, the results need to be confirmed in larger studies. The study was small, and participants were not recruited on the basis of an Alzheimer's diagnosis.

Article: Spatiotemporal characterization of Alzheimer disease pathology in living human brain tissue