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 found that TXNIP deficiency induces accelerated senescent phenotypes of mouse embryonic fibroblast (MEF) cells under high glucose condition and that the induction of cellular ROS or AKT activation is critical for cellular senescence. Our results also revealed that TXNIP inhibits AKT activity by a direct interaction, which is upregulated by high glucose and H2O2 treatment. In addition, TXNIP knockout mice exhibited an increase in glucose uptake and aging-associated phenotypes including a decrease in energy metabolism and induction of cellular senescence and aging-associated gene expression. We propose that...
Source: Fight Aging! - Category: Research Authors: Tags: Newsletters Source Type: blogs
This study sought to examine whether medical conditions which occur at a higher rate in African American individuals increase the hazard of subsequent MCI development. A secondary data analysis of the National Alzheimer's Coordinating Center Uniform Data Set was employed to examine the associations between health conditions (congestive heart failure, traumatic brain injury, diabetes, hypertension, hypercholesterolemia, B12 deficiency, thyroid disease) and their relationship to MCI. The analytic sample included 2847 participants with 9872 observations. Binary logistic generalized estimating equation modeling was used to exa...
Source: Journal of the National Medical Association - Category: General Medicine Tags: J Natl Med Assoc Source Type: research
This study evaluates how aortic stiffening relates to resting CBF and cerebrovascular reactivity (CVR) in older adults. Methods -Vanderbilt Memory &Aging Project participants free of clinical dementia, stroke, and heart failure were studied, including older adults with normal cognition (NC, n=155, 72±7, 59% male) or mild cognitive impairment (MCI, n=115, 73±7, 57% male). Aortic pulse wave velocity (PWV m/sec) was quantified from cardiac magnetic resonance. Resting CBF (mL/100g/min) and CVR (CBF response to hypercapnic normoxia stimulus) were quantified from pseudo-continuous arterial spin labeling MRI. Li...
Source: Circulation - Category: Cardiology Authors: Tags: Circulation Source Type: research
The objective here is a set of tests that (a) match up to the expected outcome based on human trials of mitochondrially targeted antioxidants, and (b) that anyone can run without the need to involve a physician, as that always adds significant time and expense. These tests are focused on the cardiovascular system, particularly measures influenced by vascular stiffness, and some consideration given to parameters relevant to oxidative stress and the development of atherosclerosis. A standard blood test, with inflammatory markers. An oxidized LDL cholesterol assessment. Resting heart rate and blood pressure. Heart r...
Source: Fight Aging! - Category: Research Authors: Tags: Newsletters Source Type: blogs
In conclusion, in the Framingham Heart Study population, in the last 30 years, disease duration in persons with dementia has decreased. However, age-adjusted mortality risk has slightly decreased after 1977-1983. Consequences of such trends on dementia prevalence should be investigated. Recent Research on the Benefits of Exercise in Later Life https://www.fightaging.org/archives/2018/04/recent-research-on-the-benefits-of-exercise-in-later-life/ A sizable body of work points to the ability of older individuals to continue to obtain benefits through regular physical activity, and particularly in the case ...
Source: Fight Aging! - Category: Research Authors: Tags: Newsletters Source Type: blogs
Fight Aging! provides a weekly digest of news and commentary for thousands of subscribers interested in the latest longevity science: progress towards the medical control of aging in order to prevent age-related frailty, suffering, and disease, as well as improvements in the present understanding of what works and what doesn't work when it comes to extending healthy life. Expect to see summaries of recent advances in medical research, news from the scientific community, advocacy and fundraising initiatives to help speed work on the repair and reversal of aging, links to online resources, and much more. This content is...
Source: Fight Aging! - Category: Research Authors: Tags: Newsletters Source Type: blogs
In conclusion, senescence of vascular cells promotes the development of age-related disorders, including heart failure, diabetes, and atherosclerotic diseases, while suppression of vascular cell senescence ameliorates phenotypic features of aging in various models. Recent findings have indicated that specific depletion of senescent cells reverses age-related changes. Although the biological networks contributing to maintenance of homeostasis are extremely complex, it seems reasonable to explore senolytic agents that can act on specific cellular components or tissues. Several clinical trials of senolytic agents are currentl...
Source: Fight Aging! - Category: Research Authors: Tags: Newsletters Source Type: blogs
CONCLUSIONS: In this large, diverse cohort, multiple measures of PPF in early adulthood to midlife were associated with dementia risk independent of smoking and vascular comorbidities. PMID: 29543604 [PubMed - as supplied by publisher]
Source: Alzheimer Disease and Associated Disorders - Category: Psychiatry Tags: Alzheimer Dis Assoc Disord Source Type: research
I often have family caregivers request medications to help people living with Alzheimer's and related dementia to sleep.By Rita JablonskiAlzheimer's Reading RoomMedications have their place in Alzheimer's care, but only AFTER all of the suggestions listed below have been followed.It may seem exhausting to the caregiver to have to engage in all of these activities; but, the resultscould lessen exhaustion, frustration, and stress in a manner of days.Subscribe to the Alzheimer's Reading - This is a Free Service - Join NowRule Out Physical Problems FirstThere are many medical conditions that contribute to problems sleeping.Som...
Source: Alzheimer's Reading Room, The - Category: Neurology Tags: alzheimers dementia connect alzheimers sleep alzheimers symptoms alzheimers treatment care of dementia patients dementia sleep not sleeping sleep medication Source Type: blogs
Fight Aging! provides a weekly digest of news and commentary for thousands of subscribers interested in the latest longevity science: progress towards the medical control of aging in order to prevent age-related frailty, suffering, and disease, as well as improvements in the present understanding of what works and what doesn't work when it comes to extending healthy life. Expect to see summaries of recent advances in medical research, news from the scientific community, advocacy and fundraising initiatives to help speed work on the repair and reversal of aging, links to online resources, and much more. This content is...
Source: Fight Aging! - Category: Research Authors: Tags: Newsletters Source Type: blogs
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