From October 22 to 24, the 23rd edition of the traditional Eibsee Meeting took place at the Eibsee Hotel in Grainau. Every year, leading scientists from all over the world gather here to exchange the latest research findings on neurodegenerative diseases such as Alzheimer’s. Despite the autumnal rainy weather, the three-day meeting began – as it has done for many years – with an informal scientific walk around the turquoise-blue Eibsee lake with a view of the colorful Alpine slopes.
After a welcome by Professor Jonas Neher, who took over the organization from Professor Christian Haass for the first time, the official program began with a series of international keynote speeches, presentations by young researchers, and a lively poster session. The topics ranged from immunological and genetic factors to biomarkers, new therapeutic approaches, and epigenetic influences in neurodegenerative diseases.
Advances and challenges in Alzheimer’s research
The scientific program was kicked off by Dr. Dennis Selkoe from Brigham and Women’s Hospital in Boston, one of the world’s most renowned Alzheimer’s researchers and co-founder of the so-called amyloid hypothesis. This hypothesis states that the misprocessing of the amyloid beta protein in the brain plays a central role in the development of Alzheimer’s disease. Selkoe pointed out that there is often a 15-year gap between the onset of harmful protein deposits—known as amyloid plaques—and the appearance of the first symptoms of dementia. This long, symptom-free phase offers a crucial therapeutic window: the earlier treatment begins, the greater the chance of slowing or halting the disease process.
Selkoe impressively demonstrated how amyloid initially forms small aggregates (oligomers) from individual protein building blocks (monomers) and finally fiber-like structures (fibrils), which condense into visible plaques. These precursors differ significantly in their toxicity to nerve cells. Recent research shows that the soluble intermediate forms, i.e., the oligomers, are particularly harmful. Based on this, Selkoe explained that modern antibody therapies, such as the recently approved drug Lecanemab, aim to recognize and neutralize precisely these early forms. For an antibody to be effective, it must precisely distinguish between the different stages of aggregation—a complex but crucial goal for drug development.
These findings mark a remarkable advance in Alzheimer’s therapy: for the first time, the underlying pathology of the disease can be directly influenced—although its effectiveness depends heavily on how early treatment begins.
New insights into mechanisms and biomarkers
The presentation by Dr. Lena Spieth (DZNE Munich) also offered exciting new perspectives. She showed that not only amyloid beta, but also apolipoprotein E (ApoE) plays a key role. This protein transports fats and cholesterol in the brain and is mainly produced by astrocytes, special support cells. The ApoE4 variant in particular is considered the greatest genetic risk factor for Alzheimer’s disease. Spieth’s team developed a mouse model to make the formation and deposition of ApoE experimentally visible. The results suggest that ApoE4 itself contributes to the formation of plaques and accelerates the disease process – an approach that could potentially be exploited in the future through complementary antibody therapies.
Nevertheless, early diagnosis remains crucial. This is why biomarkers are playing an increasingly important role. Professor Carlos Cruchaga (Washington University, St. Louis) presented results from a large-scale genetic study (GWAS) in which he and his team analyzed proteins in cerebrospinal fluid (CSF) and blood. They identified 38 proteins that are closely associated with Alzheimer’s disease, many of them involved in immune and inflammatory regulation. Particularly exciting: a combination of seven blood proteins and the established Alzheimer’s marker pTau217 can predict the course of the disease years before symptoms appear. These markers not only open up new avenues for early detection, but also serve to precisely monitor the success of therapies – such as with lecanemab – in clinical trials.
Epigenetics and the role of microglia
Dr. Sarah Marzi from King’s College London provided insight into the brain’s “epigenetic control center” in her keynote lecture. She demonstrated that genetic risk variants are often located in so-called enhancer regions—DNA segments that regulate the activity of other genes. Her analyses prove that many of these regulatory elements are active in microglia cells – the immune cells of the brain that are responsible for breaking down amyloid plaques. Marzi was also able to show that the Alzheimer’s risk gene ApoE is also controlled epigenetically, i.e., through chemical changes to the DNA. These mechanisms influence how efficiently microglia can remove pathological protein deposits.
Science award recognizes outstanding achievements
A highlight of the event was the presentation of the Hans and Ilse Breuer Publication Award, which was presented for the fifth time this year. First place was shared by Shreeya Keida (TUM & DZNE) for her study on the role of T cells in the activation of microglia in a mouse model, and Bernhard Michalowsky, who investigated the effectiveness and cost-efficiency of coordinated dementia care. The two award-winning works thus reflect the guiding principles of the foundation – the promotion of basic and care research.
Author: Ulrike Fuchs, doctoral student in Prof. André Fischer’s laboratory (DZNE Göttingen) and scholarship holder of the Hans and Ilse Breuer Foundation
