“I have lost myself, so to speak”

In a talk in 1906, Alois Alzheimer set  out the case history of his patient Auguste Deter. She had been brought to the “Institute for the Insane and Epileptic” in Frankfurt am Main, where Alzheimer was working as a senior physician, in 1901. As part of the talk, he described the typical early signs of Alzheimer’s dementia , including memory loss, disorientation, and changes in behavior and personality. Although Alzheimer had seen these symptoms in many patients before, he was puzzled by Deter because she was just 51 years old.

Alzheimer therefore began studying the patient in detail. As well as determining her general physical condition, he conducted various cognitive tests and documented them meticulously in her medical records. These tests were based on conversations that Alzheimer held with Deter, in which he set her various exercises such as naming objects and solving simple arithmetic and writing tasks. Many of these tasks are still used today as part of standardized cognitive tests for the early detection of dementia.

For a long time, the symptoms of the disease were dismissed as senile dementia. Indeed, Alzheimer himself only made a provisional diagnosis of “presenile dementia” in the case of Auguste Deter. Not content with this diagnosis, however, he continued his research. When examining Deter’s brain in the lab after her death, Alzheimer made an interesting discovery under the microscope: “Scattered throughout the cortex and particularly numerous in the upper layers, there are miliary foci due to the deposition of a peculiar substance in the cerebral cortex.” In 1984, this “peculiar substance” was identified by George Glenner and Caine Wong as an accumulation of a protein fragment known as “amyloid beta.” The question, however, was where these protein fragments came from in the first place. In 1987, a team of researchers from the University of Cologne  provided an answer by showing that beta amyloid was formed by cleavage of the amyloid precursor protein. In healthy individuals, these protein fragments are broken down by enzymes and transported out of the brain. This breakdown is disrupted in Alzheimer’s patients, causing the molecules to persist and agglomerate between nerve cells — and therefore to form “amyloid beta plaques.”

Moreover, Alzheimer observed “very peculiar changes in the neurofibrils,” which Inge Grundke-Iqbal and her colleagues sought to clarify some 80 years later. Neurofibrils are fibers within the brain cells that help to maintain the cell structure. The research group led by Grundke-Iqbal found that one key component of neurofibrils is the tau protein. This protein stabilizes transport processes within the brain, but an abnormality in Alzheimer patients causes it to become matted into bundles — known as tau fibrils — within the nerve cells. Both tau fibrils and amyloid beta plaques play a key role in the development of Alzheimer’s disease, in that they prevent nerve cells from communicating with one another and cause them to slowly die. It is still unclear why these deposits form.

PET imaging of glucose metabolism in the brain visualized the effects but not the causes of Alzheimer’s. That changed in the early 2000s, when a team of researchers at the University of Pittsburgh began developing a tracer that revealed amyloid beta plaques in the brain. In parallel, a team of scientists at Siemens were researching a biomarker that could be used to identify tau deposits. Using these tracers and modern PET/CT scanners, Alzheimer’s could now be detected early — before the damage to the brain had reached an advanced stage. The question remained, however: What use is there in detecting the disease early if there is no prospect of curing it?

It was with these moving words that, in 1994, former U.S. President Ronald Reagan concluded his letter to the public, announcing that he was suffering from Alzheimer’s. To this day, anyone receiving an Alzheimer’s diagnosis faces the same journey, in which they will lose themselves completely. There is still no cure for the disease, but there is some cause for hope: Since 2023, two antibody-based drugs have been approved in the US that target and break down amyloid beta plaques in the brain.

Rather than curing the disease, the drugs can only slow down its progression — and they are only suitable for a small group of patients with very early-stage Alzheimer’s. Moreover, the numerous side effects mean that patients must be monitored closely over the course of treatment and require regular MRI scans. Nevertheless, the drugs offer a glimmer of hope and are just one of many options currently being explored with a view to not only slowing down the disease but also, one day, finding a cure. Of course, Alzheimer’s research currently centers around understanding the disease itself, because there are many unanswered questions. With our technologies, we support researchers and accompany patients on their journey. We want to give people more time with their loved ones and help them live independently and according to their own wishes for as long as possible.