At the Institute of Neuroimmunology we study the BRAIN and processes that impair its functions.
During ageing, the brain slowly looses neurons and functional synaptical connections. However, the loss usually does not reach the levels that would impair normal functioning, since the brain has sufficient “cognitive reserve” to compensate for the lost neurons.In some of us the events take a much accelerated path, the loss of neurons overcomes the compensatory mechanisms of the brain resulting in some form of cognitive impairment. Such people suffer from neurodegeneration and are usually (~60-80% of all cases) diagnosed with dementia of Alzheimer’s type. The diseased brains contain degenerating neurons, dystrophic neurites, senile plaques and neurofibrillary tangles.
This picture was first described by a German psychiatrist Dr. Alois Alzheimer, who noticed such abnormal structures in the brain of his demised patient. Seminal studies of Dr. Heiko Braak in late 1990s have shown that number and positions of NEUROFIBRILLARY TANGLES directly correlate with neuronal loss. Molecular biology experiments, facilitated by antibodies, performed in late 1990s have shown that TANGLES are made of abnormal forms of neuronal protein TAU. At the same time, a young Slovak scientist Dr. Michal Novák working at MRC Cambridge found that TAU in those structures is TRUNCATED.
Currently, it is widely understood that two post-translational modifications, hyperphosphorylation and truncation brought about by chronic and/or acute cellular stress, induce formation of toxic, pathological conformations of TAU protein.
These abnormal TAU proteins induce a cascade of events. Due to their propensity to oligomerize, they attract normal tau molecules and other proteins, disrupt their functions and form insoluble aggregates known as paired helical filaments (PHFs) that assemble into neurofibrillary tangles. These pathological processes destabilize neuronal microtubules, impair axonal transport, increase oxidative stress, damage synapses, induce neuronal degeneration, neuroinflammation and finally death of neurons.
In order to understand the etiology of Alzheimer’s disease, we study the physiological and pathophysiological processes by investigating:
- blood-brain interactions and Alzheimer’s disease biomarkers
- structural metamorphosis of normal proteins into pathological aggregates
- immunological and neuroimmunological processes
- molecular pathways in healthy and diseased neurons
- interneuronal spreading of pathology and synaptic dysfunction
- functional alterations in healthy and diseased neurons
- strategies for regeneration of damaged neuronal tissue
- proteomics of pathogen-blood brain barrier interactions