From Alz­hei­mer’s to Hun­ting­ton’s di­sease

Hope for the early detection and treatment of neurodegenerative diseases

According to the German Alzheimer's Association, more than 1.6 million persons in Germany suffer from dementia. Owing to demographic developments, it is probable that the incidence of neurodegenerative diseases in the aging population, such as Alzheimer's and Parkinson's disease, will increase. While medical experts and basic research scientists continue to investigate Alzheimer's disease and Parkinson's diseases, they have also begun to devote their attention to rare neurodegenerative diseases, including amyotrophic lateral sclerosis, frontotemporal dementia, and Huntington's disease. These three diseases are also the focus of the DZNE site in Ulm. The central facility for this program is the Clinic for Neurology at the Rehabilitation Hospital Ulm (RKU) and Ulm University Hospital.

Deutsche Forschungsgemeinschaft (DFG)
Federal Ministry of Education and Research (BMBF)
Europäische Union (Horizon 2020)
Federal State fundings
Boehringer Ingelheim Ulm University BioCenter (BIU)
Thierry Latran Foundation
Cure Huntington's Disease Initiative Foundation (CHDI)
Endowed Professorship for Neuroanatomy of Vascular Diseases (Corona Foundation)
Endowed Professorship for Neurodegeneration (Charcot Foundation)

Boehringer Ingelheim, Biberach

Prof. Dr. Albert C. Ludolph, Clinik for Neurology

Institute of Physiological Chemistry
Prof. Dr. Thomas Wirth, Prof. Dr. Bernd Knöll
Institute of Anatomy and Cell Biology
Prof. Dr. Tobias Böckers, Prof. Dr. Nikola Golenhofen
Clinic for Neurology
Prof. Dr. Albert C. Ludolph
Clinic for Psychiatry III
Prof. Dr. Dr. Manfred Spitzer
Section for Geriatric Psychiatry
Prof. Dr. Matthias W. Riepe

Braak neuropathological stages classify the progression of widespread diseases

Forgetfulness, disorientation, and changes in personality: Alzheimer's disease is the most common form of dementia and is characterized by the presence of abnormal protein deposits in the brain. An interdisciplinary research group at Ulm University is currently investigating the pathogenesis of Alzheimer's disease-related dementia and is seeking new therapeutic approaches.

The scientific spectrum ranges from the clarification of the neuroanatomy of the disease process to its cellular mechanisms. The methods used include, among others, innovative molecular imaging and biomarker research. Ulm University Hospital has a laboratory for cerebrospinal fluid diagnostics and clinical neurochemistry for this purpose.

In cooperation with the pharmaceutical company Boehringer Ingelheim, the BIU BioCenter is studying the role of intracellular signal pathways in the development and diagnosis of Alzheimer's disease. The central focus of the Parkinson's research in Ulm is the protein alpha-synuclein, which is thought to be the cause of the disease, and the search for reliable biomarkers.

Neuroscientists are not the only ones who have contributed to an improved understanding of neurodegenerative diseases. Anatomists, biochemists, epidemiologists, and neurologists all are part of the research cohort in Ulm: Recently, with the help of cryomicroscopy, scientists at the Institute of Protein Biochemistry were able to reveal the molecular architecture of the beta-amyloid fibrils that are typical for Alzheimer's disease.

The research activities on neurodegenerative illnesses are pooled at the Neurocenter of Ulm University Hospital. Research on aging and, in particular, the "Aging Research Center Ulm University (arc uulm)" serve as overarching framework.

One of the most highly cited neuroscientists worldwide is working at the Center for Clinical Research in Ulm: Senior Professor Heiko Braak, together with Dr. Kelly Del Tredici-Braak, have continued to develop internationally used neuropathological classification schemes for Alzheimer's disease and Parkinson's disease. The progression of both illnesses has been divided into different stages based on progressive regional changes in the brain that are typical for each stage. More recently, they contributed to the development of a neuropathological staging protocol for sporadic amyotrophic lateral sclerosis.

Macroscopic overview of Alzheimer’s disease-related AT8-immunopositive tau stages in three coronal (frontal) double hemispheres of 100 µm thickness.

New DZNE site: Focus on Amyotrophic lateral sclerosis, frontotemporal dementia, Huntington’s disease

Although rarer than Alzheimer's disease and Parkinson's disease, amyotrophic lateral sclerosis (ALS,) was brought into public awareness through the ice bucket challenge and by famous personages, like the physicist Professor Stephen Hawking. The death of nerve cells controlling voluntary motor function ('motor neurons') leads to muscular atrophy and paralyses. To better understand this fatal illness, an ALS Research Center was founded in Ulm in 2013 and, together, with the German Center for Neurodegenerative Diseases (DZNE), a virtual Helmholtz Institute was established in 2013. This institution is the core of the new German Center for Neurodegenerative Diseases' (DZNE) site in Ulm, which was inaugurated early 2018. Among other things, scientists in Ulm benefit from the Swabian ALS Registry, which covers a region of over 8.4 million residents. The existence of this registry enabled neuroscientists and epidemiologists, for the first time, to calculate the prevalence of the disease in Germany.

Recent ALS research results are a cause for hope: For instance, scientists in the working groups led by Professor Albert Ludolph, Medical Director of the Clinic for Neurology, and by Professor Jochen Weishaupt have found mutations that could trigger ALS. The Clinic for Neurology is also conducting intensive research into cell biological questions and the metabolism of ALS patients. The recently proposed  neuropathological stages for ALS are also helping neurologists to better understand disease progression, to monitor it via imaging techniques for the first time, and to allow for targeted interventions in the course of the disease. Patients benefit from new, life-extending medications, deeper insights into nutrition, mechanical respiration, and improved auxiliary devices. These scientific activities in Ulm also are being supported by the Charcot Foundation, which is funded by ALS patients.

FTD is an additional focus at the new DZNE site. The breakdown of nerve cells in the frontal lobe causes dementia and often aggressive as well as socially inappropriate behavior. In contrast to Alzheimer's disease, this disorder is also found in younger persons between the ages of 50 and 60. Thus, it affects persons who are still in the workforce and in positions of responsibility. Despite its constituting up to 15% of dementia cases, many medical experts are insufficiently informed about the causes and symptoms of FTD. One of the research goals in Ulm is to determine the prevalence of FTD and to transfer the advances made in ALS research to this 'related' disorder.

Amyotrophic lateral sclerosis (ALS) causes the death of motoneurons
Amyotrophic lateral sclerosis (ALS) causes the death of motoneurons (Image: RKU Ulm)

Promising study on Huntington’s disease

Other research activities on neurodegeneration at Ulm University are focusing on Creutzfeldt-Jakob disease, for which the researchers here have developed a first blood test, as well as on the fatal genetically-linked disorder Huntington's disease. Scientists have discovered genetic variants that can influence disease onset and have elucidated the structure of the pathogenic huntingtin protein. The Clinic for Neurology at the RKU is also conducting promising clinical studies that aim to 'switch off' the huntingtin gene with an antisense drug. A nationwide register is in the making as well.

In the face of the latest demographic developments, ongoing scientific work dedicated to neurodegeneration always strives to serve future research needs: Ulm University is training the coming generations of scientists with its specialized Master's degree program in Molecular and Translational Neuroscience.

Photos: Heiko Grandel, Jesada Sabai/Shutterstock, Braak & Tel Tredici-Braak, Ktsdesign/, RKU, Lightspring/Shutterstock