The Upheaval in Alzheimer's Research and Clinical Development

It seems that the tipping point has been reached in the Alzheimer's research and development community, in the sense that it is becoming more widely accepted that new approaches are needed. The failure to produce significant benefits to patients via clearance of amyloid from the brain by immunotherapy has spurred a great deal of theorizing, and several new and promising lines of work. For example, working on restoring age-related declines in drainage of cerebrospinal fluid might remove all metabolic waste from the brain. Alternatively, a focus on neuroinflammation and the role of dysfunctional microglia is suggested, particularly by studies of senolytics showing benefits in mouse models resulting from removal of senescent microglia. The monolithic focus on amyloid is giving way to a period of greater experimentation and diversity in clinical development, and this can only be a good thing when it comes to making progress towards effective treatments for Alzheimer's disease. In the last five years, as several large clinical trials testing drugs for Alzheimer's disease failed, the field came to a stark conclusion: These approaches did nothing to slow down - let alone reverse - the course of the disease once patients already exhibited symptoms of early dementia. The failed trials, along with the dawning realization that the disease unfolds over decades, have put the entire field on a reset-to develop and test interventions that can be used much earlier, to discover new t...
Source: Fight Aging! - Category: Research Authors: Tags: Daily News Source Type: blogs

Related Links:

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
In this study, the enhanced mice live somewhat longer than their unmodified peers, though not as much longer as is the case for the application of telomerase gene therapy. The mice do also exhibit reduced cancer risk, however. The scientists here class telomere shortening as a cause of aging, which is not a point universally agreed upon. Reductions in average telomere length in tissues looks much more like a downstream consequence of reduced stem cell activity than an independent mechanism. Researchers obtain the first mice born with hyper-long telomeres and show that it is possible to extend life without any geneti...
Source: Fight Aging! - Category: Research Authors: Tags: Newsletters Source Type: blogs
People with high levels of trans fats in the blood were at higher risk for Alzheimer ’s disease and other forms of dementia.
Source: NYT Health - Category: Consumer Health News Authors: Tags: Trans Fatty Acids Alzheimer ' s Disease Cholesterol Dementia Oils and Fats Brain Source Type: news
CONCLUSION: Current state of knowledge makes the usage of cholesterol markers of cognitive decline in clinical practice impossible. PMID: 31530269 [PubMed - as supplied by publisher]
Source: Current Aging Science - Category: Geriatrics Tags: Curr Aging Sci Source Type: research
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
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
This study was aimed to estimate variations of measures of cardiovascular risk in Alzheimer's dementia by pharmacogenetic analyses of the effects of angiotensin-converting enzyme (ACE) inhibitors and statins. Methods: Consecutive patients were prospectively followed to study variations of creatinine clearance and blood pressure for one year, estimated by correlating the effects of ACE inhibitors with the ACE Alu I/D polymorphism and genotypes or haplotypes of rs1800764 or rs4291, and the effects of statins with LDLR (low-density lipoprotein receptor) genotypes or haplotypes of rs11669576 (exon 8) or rs5930 (exon 10), ...
Source: Indian J Med Res - Category: Research Authors: Tags: Indian J Med Res Source Type: research
Apolipoprotein E (APOE) is a well studied gene, given that variants are associated with a greater risk of developing Alzheimer's disease. That said, high blood pressure and high blood cholesterol levels are just as important as risk factors for Alzheimer's disease when compared against all but the worst APOE variant, APOE4. Looking beyond Alzheimer's, in most cases lifestyle choices and their consequences on the operation of metabolism, particularly becoming overweight, have larger effects on risk of age-related disease than genetic variants. The common wisdom of a 75%/25% split between environment and genetics respectivel...
Source: Fight Aging! - Category: Research Authors: Tags: Medicine, Biotech, Research Source Type: blogs
Background and Aims: HDL-like particles in human cerebrospinal fluid (CSF) promote the efflux of cholesterol from astrocytes towards the neurons that rely on this supply for their functions. Dysregulation of cerebral cholesterol homeostasis has been associated to neurodegenerative disorders, including Alzheimer's disease (AD). We evaluated whether cholesterol efflux capacity of CSF (CSF-CEC) is impaired in AD and in non-AD related dementia.
Source: Atherosclerosis - Category: Cardiology Authors: Tags: Posters 26 - 29 May, 2019 Source Type: research
More News: Alzheimer's | Brain | Cholesterol | Clinical Trials | Dementia | Immunotherapy | Neurology | PET Scan | Research | Study