Chinese nutraceuticals and physical activity; their role in neurodegenerative tauopathies

The onset of neurodegenerative disease has not only been a major cause of scientific worry, but of economic burden to the health system. This condition has been further attributed to mis-stability, deletion or mutation of tau protein, causing the onset of Corticobasal degeneration, Pick’s diseases, Progressive supranuclear palsy, Argyrophilic grains disease, Alzheimer’s diseases etc. as scientifically renowned. This is mainly related to dysregulation of translational machinery, upregulation of proinflammatory cytokines and inhibition of several essential cascades such as ERK signaling cascade, GSK3β, CREB, and PKA/PKB (Akt) signaling cascades that enhances protein processing, normal protein folding, cognitive function, and microtubule associated tau stability. Administration of some nutrients and/or bioactive compounds has a high tendency to impede tau mediated inflammation at neuronal level. Furthermore, prevention and neutralization of protein misfolding through modulation of microtubule tau stability and prevention of protein misfolding is by virtue few of the numerous beneficial effects of physical activity. Of utmost important in this study is the exploration of promising bioactivities of nutraceuticals found in china and the ameliorating potential of physical activity on tauopathies, while highlighting animal and in vitro studies that have been investigated for comprehensive understanding of its potential and an insight into the effects on human highly probable to tau mediated neurodegeneration.

Pathological Correlations of Neuropsychiatric Symptoms in Institutionalized People with Dementia

Background: Comprehensive clinicopathological studies of neuropsychiatric symptoms (NPS) in dementia are lacking. Objective: To describe the pathological correlations of NPS in a sample of institutionalized people with dementia. Methods: We studied 59 people who were consecutively admitted to a nursing home and donated their brain. Correlations between pathological variables and NPS upon admission (n = 59) and at one-year follow-up assessment (n = 46) were explored and confirmed using bivariate and multivariate statistical methods. Results: Mean (SD) age at admission was 83.2 (6.4) years and mean (SD) age at demise was 85.4 (6.6); 73% of the subjects were female and 98% presented advanced dementia. The most frequent etiological diagnosis was Alzheimer’s disease (AD; 74.6% clinical diagnosis, 67.8% pathological diagnosis). The pathological diagnosis of AD was associated with aggression (β est 0.31), depression (β est 0.31), anxiety (β est 0.38), and irritability (β est 0.28). Tau stage correlated with aggressive symptoms (β est 0.32) and anxiety (βest 0.33). Coexistence of AD and Lewy body pathology was associated with depression (β est 0.32), while argyrophilic grains were associated with eating symptoms (β est 0.29). Predictive models were achieved for apathy, including cognitive performance, basal ganglia ischemic lesions, and sex as predictors (R2 0.38) and for sleep disorders, including pathological diagnosis of AD and age at demise (R2 0.18) (all p-values <0.05, unadjusted). Conclusion: AD was the main pathological substrate of NPS in our sample of very elderly people with advanced dementia. However, correlations were mild, supporting a model of focal/asymmetric rather than diffuse brain damage, along with relevance of environmental and other personal factors, in the genesis of those symptoms.

Hysto-ultrastructure of the facial nerve and mimic muscles in the norm and in the conditions of eхperimental neuropathy

We studied the structural components of the facial nerve in the norm and with cold neuropathy, indicating morphological changes in neuromuscular endings and muscle fibers at 10, 15, 30 and 60 days from the beginning of the simulation of experimental neuropathy, which was caused by local supercooling of the projection portions of the extracranial parts of the facial nerve on the background of the preliminary introduction of Freud’s complete adjuvant. We established that the pathomorphological changes in the endonevral microcirculatory bed have a phase character: the initial spasm (up to 10 days) changes in paralytic vasodilation, and its residual effects remain until the end of the experiment (60 days). Changes in hemomicrocirculation conditions lead to marked disturbances in the structure of myelinic nerve fibers, which have the character of segmental demyelination with signs of delay in axonal transport and reactive restructuring of neuromuscular endings. The change in the metric composition of myelinated nerve fibers is due to an increase in the number of nerve fibers of medium and large diameters (up to 30 days) and small diameter (after 30 days). In different periods of the experiment, a decrease in the branching area of the terminal branches of the motor axon is observed in the nerve cells, local edema of the endonevria, degenerative changes in a part of the nerve fibers develop. Due to the fine-grained decay of the final nerve branches, degeneration of the motor endings took place two weeks after the start of the experiment. Neuropathy for 30 days caused a pronounced inhibition of spotting in the peripheral parts of the motor nerve fibers. After 60 days of experiment, a large number of muscle fibers underwent destructive changes. The size of a significant part of the neuromuscular endings was reduced. In all terms of cold neuropathy, neurolematocytes reacted in the same way: cytoplasm was swollen, argyrophilic grains appeared in the nuclei, fine-grained decay of individual nuclei occurred.

Argyrophilic grain disease: An underestimated tauopathy

Argyrophilic grain disease (AGD) is an under-recognized, distinct, highly frequent sporadic tauopathy, with a prevalence reaching 31.3% in centenarians. The most common AGD manifestation is slowly progressive amnestic mild cognitive impairment, accompanied by a high prevalence of neuropsychiatric symptoms. AGD diagnosis can only be achieved postmortem based on the finding of its three main pathologic features: argyrophilic grains, oligodendrocytic coiled bodies and neuronal pretangles. AGD is frequently seen together with Alzheimer's disease-type pathology or in association with other neurodegenerative diseases. Recent studies suggest that AGD may be a defense mechanism against the spread of other neuropathological entities, particularly Alzheimer's disease. This review aims to provide an in-depth overview of the current understanding on AGD.

Argyrophilic grain disease: An update on a frequent cause of dementia

Argyrophilic grain disease (AGD) is a sporadic, very late-onset tauopathy, accounting for approximately 4-13% of neurodegenerative dementias. AGD may manifest with a range of symptoms such as cognitive decline and behavioral abnormalities. To date, no study has been able to demonstrate a distinct clinical syndrome associated with AGD. The diagnosis is exclusively based on postmortem findings, the significance of which remains controversial because up to 30% of AGD cases are diagnosed in subjects without any cognitive impairment, while AGD findings often overlap with those of other neurodegenerative processes. Nevertheless, the presence of AGD is likely to have a significant effect on cognitive decline. The neuropathological hallmarks of AGD are argyrophilic grains, pre-neurofibrillary tangles in neurons and coiled bodies in oligodendrocytes found mainly in the entorhinal cortex and hippocampus. This review aims to provide an up-to-date overview of AGD, emphasizing pathological aspects. Additionally, the findings of a Brazilian case series are described.