New reasons for optimism in Alzheimer’s research

“In the past, learning that the symptoms you had noticed were due to early Alzheimer’s was very bleak news. In the future, it could almost become the most hopeful diagnosis among the different forms of dementia,” says Henrik Zetterberg, Professor of Neurochemistry at the University of Gothenburg.

Much of the development of these new drugs is taking place internationally, but research in Sweden and Gothenburg has made important contributions, particularly to biomarkers and early diagnosis. That expertise is becoming even more valuable as new treatments increase the need to identify, early on, which patients are most likely to benefit.

Important Swedish decision expected this fall

One treatment Henrik Zetterberg is watching particularly closely is donanemab, an antibody that targets accumulations of beta-amyloid in the brain. A health economic assessment is currently underway in Sweden.

He hopes the outcome will differ from that for lecanemab, the first drug shown to slow the progression of Alzheimer’s disease. Lecanemab has its roots in research at Uppsala University in Sweden. In April, Sweden’s New Therapies Council recommended that the country’s regions not use the drug because its cost was considered too high relative to its benefit.

Henrik Zetterberg disagrees with that assessment.

“Those of us who work in this field believe there has been some misunderstanding about how the drug should be used. The earlier you treat, the greater the effect. You also need to select the right patients, including people who do not have extensive vascular disease.”

In studies, the treatment has been shown to slow disease progression by about 30 percent on average over 18 months. But the benefit varies considerably from patient to patient, Henrik Zetterberg emphasizes.

“Some patients benefit greatly, while others do not benefit at all. That is why we need to get better at identifying the patients who will benefit from treatment.”

The two drugs also differ in how they are administered. Donanemab is given less frequently, and treatment can be discontinued once enough amyloid has been removed.

“If the New Therapies Council applies the same criteria it used for the previous drug, I think this one should receive a positive recommendation. But we don’t know what will happen this fall.”

At the forefront but still waiting

Henrik Zetterberg finds it surprising that the new treatments are not yet available through Sweden’s publicly funded healthcare system.

“Alzheimer’s research in Gothenburg and Sweden is truly at the forefront. That makes it remarkable that Swedish patients are still waiting for access to the new treatments through public healthcare, particularly since much of the research has been funded by Swedish taxpayers. We have helped generate the knowledge, yet it is being put into practice in other countries before Sweden. It is a missed opportunity.”

People with early Alzheimer’s can currently pay for lecanemab treatment at a private clinic in Stockholm. Henrik Zetterberg favors the publicly funded model but welcomes the opportunity to begin building experience with the treatment in Sweden.

Blood tests could be key

Alongside advances in treatment, diagnostic tools are developing rapidly. Gothenburg is internationally recognized for research in this area. Blood-based biomarkers could help detect the disease earlier and identify which patients are most likely to benefit from treatment.

Henrik Zetterberg envisions blood tests becoming part of memory assessments in primary care within a few years. Patients showing signs of Alzheimer’s could then be referred promptly to a memory clinic for further evaluation.

Research on Alzheimer’s disease at the University of Gothenburg spans a wide range of areas, including risk factors and early disease-related changes, brain imaging, and what happens in the brain’s neurons and synapses. The goals include gaining a better understanding of the disease, detecting it earlier, and identifying which patients may benefit from new treatments. Research from the University of Gothenburg has also contributed to the development of an active vaccine against Alzheimer’s disease, which is now being taken forward by a Gothenburg-based company and tested in clinical trials.

A brighter future

Henrik Zetterberg now divides his time between Gothenburg and the University of Wisconsin–Madison in the United States, where he studies biomarkers in large research cohorts and in relation to the new treatments that have been introduced in the US. Meanwhile, new drugs are being developed internationally that could prove more effective, easier to administer, and less likely to cause side effects.

He believes an early Alzheimer’s diagnosis could soon have a very different meaning.

“If we detect the disease early and the person does not have extensive vascular changes, we will have a good chance of slowing its progression.”

“But we must not forget the other forms of dementia. Much more research is needed there as well.”