Monitoring of diagnostically significant biomarkers of Alzheimer's disease

Alzheimer’s disease is a neurodegenerative disease of brain leading to gradually deteriorating progressive dementia. The cause of the disease still remains an unresolved question but its progression is known from neuropatophysiological findings. There is no causal treatment the disease, whose manifestation can only be slowed down. For that reason, early diagnosis can markedly improve the prognosis of patients.

During Alzheimer’s disease, the production and aggregation of pathological proteins (such as degenerative β-amyloid) occurs, and these form amyloid plaques (Fig. 1.) in the surroundings of neuronal cells. Around the plaque, sterile inflamation process is induced and within the acute reaction phase, cytokines and free oxygen radicals are released. The released molecules cause further neurodegenerative changes, e.g. peroxidation of lipids contained in the cell membrane, thus causing neuronal apoptosis. Simultaneously, changes in chemical activities of the brain take place. The synthesis of acetylcholine, a neurotrasmitter transmitting the electrical signal, is reduced. According to the latests findings, abnormalities of so-called tau proteins best correlate with the loss of neurons. Tau proteins occur mostly in the central nervous system and they stabilize microtubules. Hyperphosphorylated tau proteins bond to the loops of other tau proteins and create neurofibrillary tangles inside of the neurons (Fig. 1.). Consequently, the microtubules break down and the neuronal transport system collapses. This can first lead to disorders in chemical communication between the neurons and later to cell apoptosis.

Obr. 1 Neuron (a) in a healthy organism, (b) in an organism suffering from Alzheimer’s disease

No analytical method capable of reliable diagnostics of Alzheimer’s disease has been developed yet. Finding new biochemical markers sensitive to the changes provoked by Alzheimer’s disease in the cerebrospinal fluid can contribute to the diagnostics, progression prognosis, disease monitoring and eventually response to the treatment. One option is the monitoring of substances that play an important role in patophysiology of this disease: biomarkers of oxidation stress and neuroprostanes.