New Humanized Mouse Models Expected to Offer Greater Insights into Alzheimer’s Disease

Alzheimer’s disease is a neurodegenerative disorder that would not normally affect mice in their natural habitat. Despite this, the animals are indispensable when it comes to Alzheimer’s research. Novel mouse models are required to more clearly display the complex interactions and relations involved in Alzheimer’s disease; models that would lead to a better understanding of the causes and progression of the disease and – it is hoped – that would facilitate the development of promising therapies and would enable the disease to be diagnosed as early as possible. Researchers from the Fraunhofer Institute for Cell Therapy and Immunology IZI have now taken an important step forward in creating more appropriate mouse models. At the beginning of November, the team from Halle (Saale), Germany, attended the Society for Neuroscience’s annual meeting, where they presented for the very first time their latest advances in the development of new animal models, addressing a wide scientific audience.

Every year, the Society for Neuroscience (SfN) hosts a huge convention open to the scientific community. With close to 30,000 attendees, it is the place to be for neuroscientists from all around the world. This year’s convention was held from November 3-6 in San Diego, USA. Dr. Holger Cynis from the project group “Drug Design and Target Validation”(MWT) in Halle (Saale), Germany, attended to present Fraunhofer IZI’s latest research approaches in the development of new animal models to the assembly of international experts. Holger Cynis was one of four speakers at the SfN symposium “Global Efforts to Build More Predictive Animal Models of Neurodegenerative Disease”, which was attended by more than 500 guests from research and development.

Funded partially by one of the much-coveted New Investigator Research Grants awarded by the American Alzheimer’s Association, the Fraunhofer IZI project group has been developing mouse models where murine genes are replaced by those of humans. The replaced genes are thought to be relevant to the manifestation of Alzheimer's disease. Mice are the most commonly used animals in Alzheimer’s research in particular as their genes closely resemble those of humans. They are also easy to keep and to reproduce.

Currently, the humanized mouse models are thoroughly characterized, i.e. analyzed in detail with regard to their similarity to human pathology. Human symptoms comprise memory disturbances, disorientation and difficulties in communication as well as impaired intellectual capacity and judgment. These symptoms become more frequent as the disease progresses, making it increasingly difficult for those affected to carry out their usual day-to-day activities.

As important hallmarks of the disease, conspicuous changes have been detected in the brains of affected individuals. Here, beta-amyloid (Aβ) peptides and tau play a significant role. Aβ accumulates outside the brain cells in the form of plaques and certain forms are toxic to neurons, while tau is a protein that clumps together in the nerve cells, impairing their function. The team headed up by Dr. Holger Cynis has now succeeded, for the first time, in completely replacing the murine tau gene with its human counterpart. The scientists examined the brains of mice for 12 months in total. At the same time, behavioral tests were conducted to document their cognitive and motor performance. The researchers hope now to be able to reproduce the progression of Alzheimer’s disease better and gain a clearer understanding of the illness based on the new humanized mouse models.

A lot of research has gone into Alzheimer’s since the 1980s, with the disease first being described by German psychiatrist Dr. Alois Alzheimer in 1906. The progressive loss of memory caused by the disease is still unable to be cured or stopped today. In view of a growing and increasingly aging global population, however, it is vital that the disease is investigated as a matter of urgency. Around 50 million people suffered from Alzheimer’s disease globally at the end of 2017. According to the World Health Organization (WHO), 10 million new cases of the disease are diagnosed each year. In December last year, the organization demanded that governments and policymakers make dementia a global priority in health care policy: