The progress in understanding the pathogenesis and treatment of Alzheimer's disease (AD) is based on the recognition of the primary causes of the disease, which can be deduced from the knowledge of risk factors and biomarkers measurable in the early stages of the disease. Insights into the risk factors and the time course of biomarker abnormalities point to a role for the connection of amyloid beta (Aβ) pathology, tau pathology, mitochondrial dysfunction, and oxidative stress in the onset and development of AD. Coenzyme Q10 (CoQ10) is a lipid antioxidant and electron transporter in the mitochondrial electron transport system. The availability and activity of CoQ10 is crucial for proper mitochondrial function and cellular bioenergetics. Based on the mitochondrial hypothesis of AD and the hypothesis of oxidative stress, the regulation of the efficiency of the oxidative phosphorylation system by means of CoQ10 can be considered promising in restoring the mitochondrial function impaired in AD, or in preventing the onset of mitochondrial dysfunction and the development of amyloid and tau pathology in AD. This review summarizes the knowledge on the pathophysiology of AD, in which CoQ10 may play a significant role, with the aim of evaluating the perspective of the pharmacotherapy of AD with CoQ10 and its analogues.

• Klíčová slova
• Alzheimer’s disease, coenzyme Q10, drug, mitochondrial dysfunction, oxidative stress,
• Publikační typ
• časopisecké články MeSH
• přehledy MeSH

Damage or loss of brain cells and impaired neurochemistry, neurogenesis, and synaptic and nonsynaptic plasticity of the brain lead to dementia in neurodegenerative diseases, such as Alzheimer's disease (AD). Injury to synapses and neurons and accumulation of extracellular amyloid plaques and intracellular neurofibrillary tangles are considered the main morphological and neuropathological features of AD. Age, genetic and epigenetic factors, environmental stressors, and lifestyle contribute to the risk of AD onset and progression. These risk factors are associated with structural and functional changes in the brain, leading to cognitive decline. Biomarkers of AD reflect or cause specific changes in brain function, especially changes in pathways associated with neurotransmission, neuroinflammation, bioenergetics, apoptosis, and oxidative and nitrosative stress. Even in the initial stages, AD is associated with Aβ neurotoxicity, mitochondrial dysfunction, and tau neurotoxicity. The integrative amyloid-tau-mitochondrial hypothesis assumes that the primary cause of AD is the neurotoxicity of Aβ oligomers and tau oligomers, mitochondrial dysfunction, and their mutual synergy. For the development of new efficient AD drugs, targeting the elimination of neurotoxicity, mutual potentiation of effects, and unwanted protein interactions of risk factors and biomarkers (mainly Aβ oligomers, tau oligomers, and mitochondrial dysfunction) in the early stage of the disease seems promising.

• Klíčová slova
• Alzheimer’s disease, amyloid beta, drug, mitochondria, tau protein,
• MeSH
• Alzheimerova nemoc * metabolismus   MeSH
• amyloid metabolismus   MeSH
• amyloidní beta-protein metabolismus   MeSH
• amyloidogenní proteiny metabolismus   MeSH
• lidé MeSH
• mitochondrie metabolismus   MeSH
• Check Tag
• lidé MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH
• přehledy MeSH
• Názvy látek
• amyloid MeSH
• amyloidní beta-protein MeSH
• amyloidogenní proteiny MeSH

Dementia is a devastating age-related disorder. Its therapy would largely benefit from the identification of susceptible subjects at early, prodromal stages of the disease. To search for such prognostic markers of cognitive impairment, we studied spatial navigation in male BALBc vs. B6N mice in combination with in vivo magnetic resonance spectroscopy (1H-MRS). BALBc mice consistently showed higher escape latencies than B6N mice, both in the Water Cross Maze (WCM) and the Morris water maze (MWM). These performance deficits coincided with higher levels of myo-inositol (mIns) in the dorsal hippocampus before and after training. Subsequent biochemical analyses of hippocampal specimens by capillary immunodetection and liquid chromatography mass spectrometry-based (LC/MS) metabolomics revealed a higher abundance of glial markers (IBA-1, S100B, and GFAP) as well as distinct alterations in metabolites including a decrease in vitamins (pantothenic acid and nicotinamide), neurotransmitters (acetylcholine), their metabolites (glutamine), and acetyl-L-carnitine. Supplementation of low abundant acetyl-L-carnitine via the drinking water, however, failed to revert the behavioral deficits shown by BALBc mice. Based on our data we suggest (i) BALBc mice as an animal model and (ii) hippocampal mIns levels as a prognostic marker of mild cognitive impairment (MCI), due to (iii) local changes in microglia and astrocyte activity, which may (iv) result in decreased concentrations of promnesic molecules.

• Klíčová slova
• MCI, MRS, astrocytes, biomarker, glia, microglia, myo-inositol, spatial memory,
• Publikační typ
• časopisecké články MeSH

We aimed to explore sex differences in the association of childhood socioeconomic position (SEP) with the level of cognitive performance and the rate of cognitive decline. We studied 84,059 individuals (55% women; mean age 64 years) from the Survey on Health, Ageing and Retirement in Europe. Sex differences in the association of childhood SEP (household characteristics at age 10) with the level of cognitive performance (verbal fluency, immediate recall, delayed recall) were analysed using multilevel linear regression. Structural equation modelling tested education, depressive symptoms and physical state as mediators. The relationship between childhood socioeconomic advantage and disadvantage and the rate of cognitive decline was assessed using linear mixed-effects models. Higher childhood SEP was associated with a higher level of cognitive performance to a greater extent in women (B = 0.122; 95% CI 0.092-0.151) than in men (B = 0.109; 95% CI 0.084-0.135). The strongest mediator was education. Childhood socioeconomic disadvantage was related to a higher rate of decline in delayed recall in both sexes, with a greater association in women. Strategies to prevent impaired late-life cognitive functioning, such as reducing childhood socioeconomic disadvantages and improving education, might have a greater benefit for women.

• MeSH
• deprese psychologie   MeSH
• dítě MeSH
• kognice fyziologie   MeSH
• lidé středního věku MeSH
• lidé MeSH
• longitudinální studie MeSH
• průřezové studie MeSH
• senioři MeSH
• sexuální faktory * MeSH
• společenská třída * MeSH
• stárnutí fyziologie   MeSH
• stupeň vzdělání MeSH
• Check Tag
• dítě MeSH
• lidé středního věku MeSH
• lidé MeSH
• mužské pohlaví MeSH
• senioři MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH
• Research Support, N.I.H., Extramural MeSH