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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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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
In this study, we investigated whether Carvedilol has a neuronal protective effect against endogenous Aβ neurotoxicity in mouse Neuro2a (N2a) cells transfected with Swedish amyloid precursor protein (Swe-APP) mutant and Presenilin exon9 deletion mutant (N2a/Swe.D9). Elevated levels of reactive oxygen species (ROS), protein carbonyls, and 4-HNE were found in N2a/Swe.D9 cells, which were ameliorated by administration of Carvedilol in a dose-dependent manner. In addition, the levels of ATP and mitochondrial membrane potential were reduced in N2a/Swe.D9 cells, which were restored by treatment with Carvedilol. N2a/Swe.D9 c...
Source: Cell Stress and Chaperones - Category: Cytology Authors: Tags: Cell Stress Chaperones Source Type: research
In this study, we tested the hypothesis that Gbp1 plays a role in regulating immunometabolism and senescence of macrophages. We found that Gbp1 was mainly expressed in macrophages, but not adipocytes in response to IFNγ/LPS stimulation; Gbp1 expression was significantly decreased in inguinal white adipose tissue (iWAT) of high-fat diet (HFD)-fed and aged mice. We also observed that downregulation of Gbp1 in macrophages resulted in M1 polarization and impairment of mitochondrial respiratory function possibly via disrupting mitophagy activity. Moreover, macrophages with downregulated Gbp1 displayed dampened glycolysis ...
Source: Fight Aging! - Category: Research Authors: Tags: Newsletters Source Type: blogs
In this study, we used the Clinical Practice Research Datalink (CPRD) to estimate clinically measured SBP and DBP trajectories for 20 years prior to death, for individuals dying at 60 years and older. Second, we compared the linear SBP trends for years 10 to 3 years before death in patients who died and age- and sex-matched controls who survived at least 9 years. These approaches aimed to separate age from end-of-life associations, and avoid healthy survivor biases. Twenty years before death, estimated mean SBPs increased with increasing age at death (60-69 years, 139.5 mm Hg; ≥90 years, 150.0 mm Hg). All age-at-...
Source: Fight Aging! - Category: Research Authors: Tags: Newsletters Source Type: blogs
In this study, we integrated atomic force microscopy (AFM) and molecular approaches to determine whether increased stiffness of aortic VSMCs in hypertensive rats is ROCK-dependent, and whether the anti-hypertensive effect of ROCK inhibitors contributes to the reduction of aortic stiffness via changing VSMC mechanical properties. Despite a widely held belief that aortic stiffening is associated with changes in extracellular matrix proteins and endothelial dysfunction, our recent studies demonstrated that intrinsic stiffening of aortic VSMCs, independent of VSMC proliferation and migration, is an important contributo...
Source: Fight Aging! - Category: Research Authors: Tags: Newsletters Source Type: blogs
In conclusion, we have developed an effective PILs strategy to deliver the AUF1 plasmid to a specific target, and this system may be useful for the development of new anti-aging drugs. Considering the Evidence for Vascular Amyloidosis as a Cause of Aging https://www.fightaging.org/archives/2017/11/considering-the-evidence-for-vascular-amyloidosis-as-a-cause-of-aging/ The balance of evidence for the aging of the cardiovascular system suggests the following view. It starts off in the blood vessels, with the accumulation of senescent cells and cross-links. Cross-links directly stiffen these tissues, while ...
Source: Fight Aging! - Category: Research Authors: Tags: Newsletters Source Type: blogs
ObjectiveTo investigate the associations between age, vascular health, and Alzheimer disease (AD) imaging biomarkers in an elderly sample. MethodsWe identified 430 individuals along the cognitive continuum aged>60 years with amyloid positron emission tomography (PET), tau PET, and magnetic resonance imaging (MRI) scans from the population‐based Mayo Clinic Study of Aging. A subset of 329 individuals had fluorodeoxyglucose (FDG) PET. We ascertained presently existing cardiovascular and metabolic conditions (CMC) from health care records and used the summation of presence/absence of hypertension, hyperlipidemia, cardiac...
Source: Annals of Neurology - Category: Neurology Authors: Tags: Research Article Source Type: research
In this study, we demonstrate that irrespective of the derivation of CD8+ CD45RA+CD27- T cells, these primed cells exhibit a unique highly inflammatory secretory profile characteristic of the SASP, and we also provide evidence that ADAM28 can be used as a functional marker of senescence in CD8+ T cells. Furthermore, we show that the secretory phenotype in CD8+ CD45RA+CD27- T cells is controlled through p38 MAPK signalling, which contributes to age-associated inflammation. Patient Paid Clinical Studies are a Good Plan for Rejuvenation Therapies https://www.fightaging.org/archives/2017/10/patient-paid-clinical-st...
Source: Fight Aging! - Category: Research Authors: Tags: Newsletters Source Type: blogs
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Source: Annals of Neurology - Category: Neurology Authors: Tags: Research Article Source Type: research
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