scholarly journals Clinical and Biophysical Principles of Vascular Dementia and Alzheimer’s Disease Treatment

2019 ◽  
Vol 5 (5) ◽  
pp. 57-72 ◽  
Author(s):  
S. Bulgakova ◽  
P. Romanchuk ◽  
A. Volobuev
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Vascular Dementia ◽  
Hippocampal Neurons ◽  
Structural Changes ◽  
Neuronal Damage ◽  
Oxidant Stress ◽  
Cerebral Hypoperfusion ◽  
Term Care ◽  
Β Amyloid

Biophysics of blood circulation in Alzheimer’s disease is characterized by disorders of laminar blood flow and cerebral hypoperfusion. As a result, failure intracellular metabolism, there is a cascade of changes in neurons associated with the processes of excitotoxicity and oxidant stress, which in turn stimulates amyloidogenesis. Experimental and 25-year observations have shown that the long-existing state of hypoperfusion leads to hippocampal disorders. This process is accompanied by memory impairment, structural changes in the capillaries in the hippocampus, impaired glucose and protein metabolism, β–amyloid deposition, activation of glial tissue, death of hippocampal neurons. Neuroreflex disruption in the ‘cerebral heart’ and a violation of cerebrovascular homeostasis contributes to the development of vascular dementia through the following mechanisms, including cerebral microangiopathy, endothelial dysfunction, oxidative stress, neuronal damage, the increase in β–amyloid neurotoxicity, apoptosis, etc. The duration of therapy with antiglutamatergic and multimodal drugs in Alzheimer’s disease requires constant multidisciplinary monitoring of targets and medical and social control in the system of long-term care. Lifelong acquisition of knowledge, information positive Nano communication enable the preservation of mental health and active longevity. Innovative methods of P4-medicine of neuroplasticity management allow to carry out timely prevention of the factors reducing neuroplasticity, to keep factors of positive influence on visceral and cognitive brain, and the main thing — in due time to apply in practical health care the combined methods of preservation and development of the human cognitive brain.

scholarly journals Biophysics of Blood Circulation in Vascular Dementia and Alzheimer’s Disease

2019 ◽  
Vol 5 (4) ◽  
pp. 76-102 ◽  
Author(s):  
A. Volobuev ◽  
P. Romanchuk
Keyword(s):  
Alzheimer’S Disease ◽  
Blood Pressure ◽  
Alzheimer's Disease ◽  
Blood Flow ◽  
Vascular Dementia ◽  
Blood Circulation ◽  
Oxidant Stress ◽  
Cerebral Hypoperfusion ◽  
Adequate Treatment ◽  
Small Vessels

Modern rational pharmacotherapy allows being provided with a balance of efficacy and safety in clinical geriatrics, which is especially important in patients with neurovascular degeneration, including in the presence of severe forms of vascular comorbidity, requiring multi–component therapy, under the condition of active multidisciplinary and interdepartmental impact. Dementia in its origin is mixed and it is extremely difficult to divide into parts its primary degenerative or vascular component. The differentiated approach is determined by the heterogeneity of the pathological process, which common is the relationship of cerebral vascular damages with the development of the brain symptoms damage. The problem of nosological independence of Alzheimer’s disease is the subject of discussion for patients of older age groups (especially in people 65 years and older). The genesis of mnestic–intellectual disorders is due not so much to primary–degenerative as vascular changes, especially at the level of the microcirculatory canal. The modern problem of neurodegeneration has a neurophysiological, biophysical, gerontological, geriatric and strategic practical orientation since the diagnosis of the cause of the disease determines the choice of adequate treatment. Due to a large number of pathogenetical mechanisms, there is no single and standardized method of treatment for vascular dementia and Alzheimer’s disease. In any case, prevention of the development and progression of vascular dementia and Alzheimer’s disease should take into account the etiological mechanisms of its occurrence, because it will vary in patients with failures of small vessels, occlusive damages of the main arteries of the head or an embolism of cardiogenic origin. In patients with failures of small vessels, the main direction of therapy should be the normalization of blood pressure, which leads to improved cognitive functions. At the same time, excessive lowering of blood pressure can provoke an increase in mnestic-intellectual disorders, possibly caused by a secondary decrease in cerebral blood flow due to a violation of autoregulation. Biophysics of blood circulation in Alzheimer’s disease is characterized by disorders of laminar blood flow and cerebral hypoperfusion. As a result, failure intracellular metabolism, there is a cascade of changes in neurons associated with the processes of excitotoxicity and oxidant stress, which in turn stimulates amyloidogenesis. Experimental and 25-year observations have shown that the long–existing state of hypoperfusion leads to hippocampal disorders. This process is accompanied by memory impairment, structural changes in the capillaries in the hippocampus, impaired glucose and protein metabolism, β–amyloid deposition, activation of glial tissue, the death of hippocampal neurons.

scholarly journals Stabilization of dynamic microtubules by mDia1 drives Tau-dependent Aβ1–42 synaptotoxicity

2017 ◽  
Vol 216 (10) ◽  
pp. 3161-3178 ◽  
Author(s):  
Xiaoyi Qu ◽  
Feng Ning Yuan ◽  
Carlo Corona ◽  
Silvia Pasini ◽  
Maria Elena Pero ◽  
...  
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Axonal Transport ◽  
Dendritic Spines ◽  
Posttranslational Modifications ◽  
Hippocampal Neurons ◽  
Neuronal Damage ◽  
Driving Factors ◽  
Hyperphosphorylated Tau ◽  
Tau Hyperphosphorylation

Oligomeric Amyloid β1–42 (Aβ) plays a crucial synaptotoxic role in Alzheimer’s disease, and hyperphosphorylated tau facilitates Aβ toxicity. The link between Aβ and tau, however, remains controversial. In this study, we find that in hippocampal neurons, Aβ acutely induces tubulin posttranslational modifications (PTMs) and stabilizes dynamic microtubules (MTs) by reducing their catastrophe frequency. Silencing or acute inhibition of the formin mDia1 suppresses these activities and corrects the synaptotoxicity and deficits of axonal transport induced by Aβ. We explored the mechanism of rescue and found that stabilization of dynamic MTs promotes tau-dependent loss of dendritic spines and tau hyperphosphorylation. Collectively, these results uncover a novel role for mDia1 in Aβ-mediated synaptotoxicity and demonstrate that inhibition of MT dynamics and accumulation of PTMs are driving factors for the induction of tau-mediated neuronal damage.

scholarly journals Lipid Peroxidation in Chronic Cerebral HypoperfusionInduced Neurodegeneration in Rats

2020 ◽  
Vol 10 (2) ◽  
Author(s):  
Anil Kumar S ◽  
Saif SA ◽  
Oothuman P ◽  
Mustafa MIA
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Lipid Peroxidation ◽  
Neurodegenerative Disorders ◽  
Neuronal Damage ◽  
Neuronal Cell ◽  
Chronic Cerebral Hypoperfusion ◽  
Cerebral Hypoperfusion ◽  
Control Group ◽  
Vessel Occlusion

Introduction: Reduced cerebral blood fl ow is associated with neurodegenerative disorders and dementia, in particular. Experimental evidence has demonstrated the initiating role of chronic cerebral hypoperfusion in neuronal damage to the hippocampus, the cerebral cortex, the white matter areas and the visual system. Permanent, bilateral occlusion of the common carotid arteries of rats (two vessel occlusion - 2VO) has been introduced for the reproduction of chronic cerebral hypoperfusion as it occurs in Alzheimer’s disease and human aging. Increased generation of free radicals through lipid peroxidation can damage neuronal cell membrane. Markers of lipid peroxidation have been found to be elevated in brain tissues and body fl uids in neurodegenerative diseases, including Alzheimer’s disease, Parkinson disease and amyotrophic lateral sclerosis. Materials and Methods: Malondialdehyde (MDA), final product of lipid peroxidation, was estimated by thiobarbituric acid-reactive substances (TBARS) assay kit at eight weeks after induction of 2VO in the rats and control group. Results: Our study revealed a highly signifi cant (p<0.001) increase in the mean MDA concentration (12.296 ± 1.113 μM) in 2VO rats as compared to the control group (5.286 ± 0.363 μM) rats. Conclusion: Therapeutic strategies to modulate lipid peroxidation early throughout the course of the disease may be promising in slowing or possibly preventing neurodegenerative disorders.

Improved diagnostic discrimination of patients with Alzheimer's disease and vascular dementia using tau and β-amyloid(1–42) levels in CSF

2000 ◽  
Vol 21 ◽  
pp. 227
Author(s):  
Ruediger Mielke ◽  
Michael Strohmeier ◽  
Marko Nekic ◽  
Stefan Bamborschke ◽  
Joachim Behrendt ◽  
...  
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Vascular Dementia ◽  
Β Amyloid

scholarly journals Ganoderma lucidum Triterpenoids (GLTs) Reduce Neuronal Apoptosis via Inhibition of ROCK Signal Pathway in APP/PS1 Transgenic Alzheimer’s Disease Mice

2020 ◽  
Vol 2020 ◽  
pp. 1-11
Author(s):  
Nanhui Yu ◽  
Yongpan Huang ◽  
Yu Jiang ◽  
Lianhong Zou ◽  
Xiehong Liu ◽  
...  
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Cognitive Impairment ◽  
Signaling Pathway ◽  
Ganoderma Lucidum ◽  
Hippocampal Neurons ◽  
Caspase 3 ◽  
Neuronal Damage ◽  
Tunel Staining ◽  
Ganoderma Lucidum Triterpenoids

Alzheimer’s disease (AD) is the most common cause of dementia among senior citizen. Ganoderma lucidum triterpenoids (GLTs) have nutritional health benefits and has been shown to promote health and longevity, but a protective effect of GLTs on AD damage has not yet been reported. The objective of this research was to elucidate the phylactic effect of GLTs on AD model mice and cells and to explore its underlying mechanisms. Morris water maze (MWM) test was conducted to detect changes in the cognitive function of mice. Hematoxylin-eosin (HE) staining was applied to observe pathological changes in the hippocampus. Silver nitrate staining was applied to observe the hippocampal neuronal tangles (NFTs). Apoptosis of the hippocampal neurons in mouse brain tissue was determined by TUNEL staining. The expression levels of apoptosis-related protein Bcl2, Bax, and caspase 3/cleaved caspase 3; antioxidative protein Nrf2, NQO1, and HO1; and ROCK signaling pathway-associated proteins ROCK2 and ROCK1 were measured by western blot. In vivo experiments show that 5-month-old APP/PS1 mice appeared to have impaired acquisition of spatial learning and GLTs could reduce cognitive impairment in AD mice. Compared to normal mice, the hippocampus of APP/PS1 mouse’s brains was severely damaged, while GLTs could alleviate this symptom by inhibiting apoptosis, relieving oxidative damage, and inactivating the ROCK signaling pathway. In in vitro cell experiments, Aβ25-35 was applied to induce hippocampal neurons into AD model cells. GLTs promoted cell proliferation, facilitated superoxide dismutase (SOD) expression, and inhibited malondialdehyde (MDA) and lactic dehydrogenase (LDH) expression of neurons. Our study highlights that GLTs improve cognitive impairment, alleviate neuronal damage, and inhibit apoptosis in the hippocampus tissues and cells in AD through inhibiting the ROCK signaling pathway.

scholarly journals Linking Oxidative Stress and Proteinopathy in Alzheimer’s Disease

Antioxidants ◽  
2021 ◽  
Vol 10 (8) ◽  
pp. 1231
Author(s):  
Chanchal Sharma ◽  
Sang Ryong Kim
Keyword(s):  
Oxidative Stress ◽  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Structural Changes ◽  
Aging Brain ◽  
Ros Production ◽  
Subsequent Loss ◽  
Β Amyloid ◽  
Neuroprotective Therapies

Proteinopathy and excessive production of reactive oxygen species (ROS), which are the principal features observed in the Alzheimer’s disease (AD) brain, contribute to neuronal toxicity. β-amyloid and tau are the primary proteins responsible for the proteinopathy (amyloidopathy and tauopathy, respectively) in AD, which depends on ROS production; these aggregates can also generate ROS. These mechanisms work in concert and reinforce each other to drive the pathology observed in the aging brain, which primarily involves oxidative stress (OS). This, in turn, triggers neurodegeneration due to the subsequent loss of synapses and neurons. Understanding these interactions may thus aid in the identification of potential neuroprotective therapies that could be clinically useful. Here, we review the role of β-amyloid and tau in the activation of ROS production. We then further discuss how free radicals can influence structural changes in key toxic intermediates and describe the putative mechanisms by which OS and oligomers cause neuronal death.

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