Towards Immunotherapies Targeting Both Amyloid- β and Tau in Alzheimer's Disease

Clearing amyloid-β from the brain has failed to reverse Alzheimer's disease in patients, and this unfortunate outcome is slowly - all too slowly - producing a change in direction in the mainstream of Alzheimer's research. One possible conclusion is that amyloid-β is simply the wrong target, and this has led to a great deal of alternative theorizing in recent years. Even so, the consensus remains that amyloid-β does play a significant role in the condition, albeit not enough of a role in the later stages of Alzheimer's to allow anti-amyloid therapies to work. The jury remains out on whether early reduction in amyloid-β aggregation can postpone Alzheimer's - i.e. whether this aggregation actually a causative mechanism or whether it is a side-effect of the actual cause, such as chronic inflammation driven by persistent infection. A currently popular view is that the mechanistic evidence continues to suggest that amyloid-β is important, and thus it should be targeted - but not in isolation, as the past decade or two of failed trials amply demonstrate that removal of only amyloid-β is not sufficient. The conclusion is that there must also be reductions in tau aggregation, perhaps treatment of cerebrovascular dysfunction, suppression of inflammation in the brain, and so forth. Along these lines, today's open access research is a demonstration of a combination immunotherapy in mice that targets both amyloid-β and tau. Absent stunning success...
Source: Fight Aging! - Category: Research Authors: Tags: Medicine, Biotech, Research Source Type: blogs

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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
This study provides strong evidence that following a healthy lifestyle can substantially extend the years a person lives disease-free." Commentary on Recent Evidence for Cognitive Decline to Precede Amyloid Aggregation in Alzheimer's Disease https://www.fightaging.org/archives/2020/01/commentary-on-recent-evidence-for-cognitive-decline-to-precede-amyloid-aggregation-in-alzheimers-disease/ I can't say that I think the data presented in the research noted here merits quite the degree of the attention that it has been given in the popular science press. It is interesting, but not compelling if its role...
Source: Fight Aging! - Category: Research Authors: Tags: Newsletters Source Type: blogs
(Flinders University) A vaccine to ward off dementia may proceed to clinical trials after successful animal testing. The US-led research is looking to develop effective immunotherapy via a dual vaccine to remove 'brain plaque' and tau protein aggregates linked to Alzheimer's disease. It is showing success in begenic mice models, supports progression to human trials in years to come.
Source: EurekAlert! - Medicine and Health - Category: International Medicine & Public Health Source Type: news
This study demonstrates for the first time that senescent cells secrete functional LTs, significantly contributing to the LTs pool known to cause or exacerbate idiopathic pulmonary fibrosis. Against Senolytics https://www.fightaging.org/archives/2019/11/against-senolytics/ There is no consensus in science that is so strong as to have no heretics. So here we have an interview with a naysayer on the matter of senolytic treatments, who argues that the loss of senescent cells in aged tissues will cause more harm to long-term health than the damage they will do by remaining. To be clear, I think this to be a ...
Source: Fight Aging! - Category: Research Authors: Tags: Newsletters Source Type: blogs
This study elucidates the potential to use mitochondria from different donors (PAMM) to treat UVR stress and possibly other types of damage or metabolic malfunctions in cells, resulting in not only in-vitro but also ex-vivo applications. Gene Therapy in Mice Alters the Balance of Macrophage Phenotypes to Slow Atherosclerosis Progression https://www.fightaging.org/archives/2019/07/gene-therapy-in-mice-alters-the-balance-of-macrophage-phenotypes-to-slow-atherosclerosis-progression/ Atherosclerosis causes a sizable fraction of all deaths in our species. It is the generation of fatty deposits in blood vessel...
Source: Fight Aging! - Category: Research Authors: Tags: Newsletters Source Type: blogs
In this study, we found that cofilin competes with tau for direct microtubule binding in vitro, in cells, and in vivo, which inhibits tau-induced microtubule assembly. Genetic reduction of cofilin mitigates tauopathy and synaptic defects in Tau-P301S mice and movement deficits in tau transgenic C. elegans. The pathogenic effects of cofilin are selectively mediated by activated cofilin, as active but not inactive cofilin selectively interacts with tubulin, destabilizes microtubules, and promotes tauopathy. These results therefore indicate that activated cofilin plays an essential intermediary role in neurotoxic signaling th...
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
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 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
In this study, we analyzed FGF21 levels and alterations in the expression of genes encoding components of the FGF21-responsive molecular machinery in adipose tissue from aged individuals so as to ascertain whether altered FGF21 responsiveness that develops with aging jeopardizes human health and/or accelerates metabolic disturbances associated with aging. We studied a cohort of 28 healthy elderly individuals (≥70 years) with no overt signs of metabolic or other pathologies and compared them with a cohort of 35 young healthy controls (≤40 years). Serum FGF21 levels were significantly increased in elderly indiv...
Source: Fight Aging! - Category: Research Authors: Tags: Newsletters Source Type: blogs
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