Evidence for Tau Accumulation and Failing Cerebrospinal Fluid Clearance to be the Starting Point for Alzheimer's Disease

Alzheimer's disease might be considered as the consequence of the related, interacting buildup of two primary forms of metabolic waste in the brain, tau and amyloid-β. Either, independently, can cause neurodegeneration, but they have a complicated relationship with one another in which the presence of both makes the pathology worse. Which comes first? There is evidence to suggest that amyloid aggregation leads to tau aggregation, and there is also evidence for things to be the other way around, such as that presented in the research materials here. Both of these options could be the case, in that either tau or amyloid-β produces disruption that can accelerate aggregation of the other. Or it may be that a third mechanism, such as loss of effective drainage of cerebrospinal fluid, causes aggregation of both, and interactions between the two are less important to the amount present and more important to the damage done. Alzheimer's is a very complex area of study. Until therapies start to make some inroads into improving the condition, thereby quantifying some of the mechanisms and their effects, it is likely that greater understanding of the details of the progression of the condition, and the degree to which different aspects contribute to cognitive decline, will be slow to arrive. In the commonly held definition of Alzheimer's disease, one type of amyloid-beta (Aβ42) starts to form clumps between nerve cells, injuring them. Worsening injury is ...
Source: Fight Aging! - Category: Research Authors: Tags: Daily News Source Type: blogs

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In this study, we hypothesized that moderately and chronically reducing ACh could attenuate the deleterious effects of aging on NMJs and skeletal muscles. To test this hypothesis, we analyzed NMJs and muscle fibers from heterozygous transgenic mice with reduced expression of the vesicular ACh transporter (VAChT), VKDHet mice, which present with approximately 30% less synaptic ACh compared to control mice. Because ACh is constitutively decreased in VKDHet, we first analyzed developing NMJs and muscle fibers. We found no obvious morphological or molecular differences between NMJs and muscle fibers of VKDHet and contro...
Source: Fight Aging! - Category: Research Authors: Tags: Newsletters Source Type: blogs
In humans, oxidative stress is involved in the development of diabetes, cancer, hypertension, Alzheimers' disease, and heart failure. One of the mechanisms in the cellular defence against oxidative stress is the activation of the Nrf2-antioxidant response element (ARE) signalling pathway. Computation of activity, efficacy, and potency score of ARE signalling pathway and to propose a multi-level prediction scheme for the same is the main aim of the study as it contributes in a big amount to the improvement of oxidative stress in humans. Applying the process of knowledge discovery from data, required knowledge is gathered an...
Source: IET Systems Biology - Category: Biology Source Type: research
Discussion of Developmental Effects on Aging Microtubule Function and Longevity in Nematodes Quantifying the Correlation Between Poverty and Faster Pace of Aging Matthew O'Connor Presenting on Underdog Pharmaceuticals at Undoing Aging 2019 https://www.fightaging.org/archives/2019/09/matthew-oconnor-presenting-on-underdog-pharmaceuticals-at-undoing-aging-2019/ Here Matthew O'Connor of the SENS Research Foundation talks about the research that led to founding of Underdog Pharmaceuticals, a biotech startup incubated by the foundation to commercialize a means of targeting 7-ketocholesterol in atheroscleros...
Source: Fight Aging! - Category: Research Authors: Tags: Newsletters Source Type: blogs
In this study, researchers studied 438,952 participants in the UK Biobank, who had a total of 24,980 major coronary events - defined as the first occurrence of non-fatal heart attack, ischaemic stroke, or death due to coronary heart disease. They used an approach called Mendelian randomisation, which uses naturally occurring genetic differences to randomly divide the participants into groups, mimicking the effects of running a clinical trial. People with genes associated with lower blood pressure, lower LDL cholesterol, and a combination of both were put into different groups, and compared against those without thes...
Source: Fight Aging! - Category: Research Authors: Tags: Newsletters Source Type: blogs
Publication date: Available online 10 September 2019Source: SteroidsAuthor(s): Matthias Barton, Matthias R. Meyer, Eric R. ProssnitzAbstractChronic non-communicable diseases share the pathomechanism of increased reactive oxygen species (ROS) production by nicotinamide adenine dinucleotide phosphate (NADPH) oxidases, known as Nox. The recent discovery that expression of Nox1, a Nox isoform that has been implicated in the pathogenesis of cardiovascular and kidney disease, is regulated by the expression and activity of G protein-coupled estrogen receptor (GPER) led to the identification of orally active small-molecule GPER bl...
Source: Steroids - Category: Drugs & Pharmacology Source Type: research
We examined human lung tissue from COPD patients and normal control subjects, and found a substantial increase in p16-expressing alveolar cells in COPD patients. Using a transgenic mouse deficient for p16, we demonstrated that lungs of mice lacking p16 were structurally and functionally resistant to CS-induced emphysema due to activation of IGF1/Akt regenerative and protective signaling. Fat Tissue Surrounds Skeletal Muscle to Accelerate Atrophy in Aging and Obesity https://www.fightaging.org/archives/2019/09/fat-tissue-surrounds-skeletal-muscle-to-accelerate-atrophy-in-aging-and-obesity/ Researchers her...
Source: Fight Aging! - Category: Research Authors: Tags: Newsletters Source Type: blogs
In conclusion, in the absence of obesity, visceral adipose tissue possesses a pronounced anti-inflammatory phenotype during aging which is further enhanced by exercise. Methods of Inducing Cellular Damage are Rarely Relevant to Aging, and the Details Matter https://www.fightaging.org/archives/2019/08/methods-of-inducing-cellular-damage-are-rarely-relevant-to-aging-and-the-details-matter/ One of the major challenges in aging research is determining whether or not models of cellular or organismal damage and its consequences are in any way relevant to the natural processes of aging. One can hit a brick with...
Source: Fight Aging! - Category: Research Authors: Tags: Newsletters Source Type: blogs
Fight Aging! publishes news and commentary relevant to the goal of ending all age-related disease, to be achieved by bringing the mechanisms of aging under the control of modern medicine. This weekly newsletter is sent to thousands of interested subscribers. To subscribe or unsubscribe from the newsletter, please visit: https://www.fightaging.org/newsletter/ Longevity Industry Consulting Services Reason, the founder of Fight Aging! and Repair Biotechnologies, offers strategic consulting services to investors, entrepreneurs, and others interested in the longevity industry and its complexities. To find out m...
Source: Fight Aging! - Category: Research Authors: Tags: Newsletters Source Type: blogs
Authors: Wanleenuwat P, Iwanowski P, Kozubski W Abstract Alzheimer's disease (AD) is the most common form of dementia manifesting as alterations in cognitive abilities, behavior and deterioration in memory which is progressive, leading to gradual worsening of symptoms. Major pathological features of AD are accumulations of neuronal amyloid plaques and neurofibrillary tangles, with early lesions appearing primarily in the hippocampus, the area of the brain involved in memory and learning. Cardiovascular related risk factors are believed to play a crucial role in disease development and the acceleration of cognitive ...
Source: Postgraduate Medicine - Category: Internal Medicine Tags: Postgrad Med Source Type: research
In conclusion, with study of the frailty syndrome still in its infancy, frailty analysis remains a major challenge. It is a challenge that needs to be overcome in order to shed light on the multiple mechanisms involved in the pathogenesis of this syndrome. Although several mechanisms contribute to frailty, immune system alteration seems to play a central role: this syndrome is characterized by increased levels of pro-inflammatory markers and the resulting pro-inflammatory status can have negative effects on various organs. Future studies should aim to better clarify the immune system alteration in frailty, and seek to esta...
Source: Fight Aging! - Category: Research Authors: Tags: Newsletters Source Type: blogs
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