Projects

T-POT

Alzheimer's disease is one of the greatest challenges of the 21st century. Understanding its causes, developing effective therapies for those affected and defining preventive measures are integral parts of the research mission of the Neurodegeneration Department. Effective therapy development requires a better understanding of the disease, to which our T-POT study (Tau Propagation over Time) is intended to contribute.

Increased protein accumulations (protein clumps) in the brain are a key feature of neurodegenerative diseases such as Alzheimer's dementia. In Alzheimer's disease, two forms of these protein clumps are particularly well known and are discussed as possible causes of the disease: the so-called tau deposits (also known as “tangles” or “neurofibrils”) and the -amyloid deposits (also known as “plaques”). It is now assumed that these clumps spread through the brain's networks over time and impair their function.

As Alzheimer's disease occurs late in life and in most cases is not caused by a genetic mutation, it is assumed that the disease is influenced by gene-environment interactions. Environmental influences on our genes, which are responsible for the production of proteins, can be measured in the blood. Differences in this aspect have already been identified between patients with Alzheimer's disease and healthy individuals. It is assumed that these differences play a role in the accumulation of pathological protein clumps.

Apart from this, it has been shown that individuals who have engaged in mentally stimulating activities throughout their lives show altered network functions and disease progression. This could prove to be important for the clinical diagnosis and course of the disease.

The aim of our overall study is therefore to identify and characterize the protein clump spread and the loss of functional brain networks in different phases and over the course of the disease using various brain imaging methods. Therefore, the participants are neuropsychologically examined at the beginning of the study and after 18 months. Positron emission tomography (PET) is used to visualize the amyloid and tau protein clumps, and magnetic resonance imaging (MRI) is used to record the function of the cranial nerve networks at both study time points. Blood samples are taken to record gene-environment interactions, and information on previous lifestyle is collected.

As part of T-POT, we have established two optional additional modules that cover further key research areas:

T-POT Sleep

In “T-POT Sleep”, we are investigating further aspects of Alzheimer's disease in collaboration with the “Molecular Plasticity” Department at INM-2. In this sub-study, the duration and quality of sleep will be examined using a headband in order to gain insights into how various sleep parameters can affect the development of Alzheimer's disease.

In the “T-POT Motor” sub-study, the focus rests on the investigation of motor movement sequences, as these can also be impaired in some people affected by Alzheimer's disease. This sub-study is being carried out in collaboration with the Department of Nuclear Medicine and the Department of Neurology at Cologne University Hospital.

T-POT is a multi-center, prospective, long-term study. The study has been funded by the German Research Foundation since 2017 and is expected to continue until the end of 2025.

DoMoCo

Parkinson's disease is the second most common neurodegenerative disease after Alzheimer's disease. It is mainly characterized by motor, but also cognitive symptoms. The loss of the neurotransmitter “dopamine” is probably the reason for these symptoms. In the DoMoCo study, we are investigating the role of dopamine with regard to voluntary movement and cost-benefit calculations during movement.

When performing a voluntary movement, a number of processes are activated in our brain before the actual movement occurs: It is considered how and when this movement should be performed (planning), whether it is worth performing this movement (cost-benefit analysis) and how forcefully this movement should be performed (strength). The neurotransmitter dopamine plays an important role in this. However, it is not yet known to what extent this neurotransmitter influences the planning, cost-benefit analysis and strength of the movement. Furthermore, we do not yet know exactly which networks (functional connections between different regions in the brain) are activated. The investigation of these functions is particularly important with regard to diseases of the motor system, such as Parkinson's disease. This disease is characterized by the loss of the neurotransmitter dopamine and is associated with various motor impairments, such as slower execution of a movement. However, the consequences for the individual processes of movement (planning, cost-benefit analysis, strength) due to the loss of the neurotransmitter dopamine are not equally expressed in each person. In particular, the long prodromal phase of Parkinson's disease (i.e. the time in which no symptoms are recognized but the disease has already begun) indicates that the loss of the neurotransmitter dopamine can be compensated for. The extent of compensation mechanisms varies from person to person and is probably related to a kind of “motor reserve” that is influenced by lifestyle factors. The influence of motor reserve has not yet extensively been studied, but plays an important role in the clinical picture and course of Parkinson's disease. Using brain imaging techniques, we can now measure both the neurotransmitter dopamine and the activation of different brain areas during movement. By using these imaging techniques, we can thus: 1) investigate the role of different domains (i.e. planning, cost-benefit analysis, strength) for the execution of a movement, 2) identify different functional networks that are active during the execution of a movement, 3) observe the role of dopamine in this respect, and 4) investigate the influence of motor reserve, especially in Parkinson's disease.

This is a multi-center, prospective observational study. The study is funded by the German Research Foundation (Collaborative Research Center SFB 1451) and will be conducted until the end of 2024.

Last Modified: 25.09.2024