Early Life Stress and Epigenetics in Late-onset Alzheimer's Dementia: A Systematic Review.

Early Life Stress and Epigenetics in Late-onset Alzheimer's Dementia: A Systematic Review. Curr Genomics. 2018 Nov;19(7):522-602 Authors: Lemche E Abstract Involvement of life stress in Late-Onset Alzheimer's Disease (LOAD) has been evinced in longitudinal cohort epidemiological studies, and endocrinologic evidence suggests involvements of catecholamine and corticosteroid systems in LOAD. Early Life Stress (ELS) rodent models have successfully demonstrated sequelae of maternal separation resulting in LOAD-analogous pathology, thereby supporting a role of insulin receptor signalling pertaining to GSK-3beta facilitated tau hyper-phosphorylation and amyloidogenic processing. Discussed are relevant ELS studies, and findings from three mitogen-activated protein kinase pathways (JNK/SAPK pathway, ERK pathway, p38/MAPK pathway) relevant for mediating environmental stresses. Further considered were the roles of autophagy impairment, neuroinflammation, and brain insulin resistance. For the meta-analytic evaluation, 224 candidate gene loci were extracted from reviews of animal studies of LOAD pathophysiological mechanisms, of which 60 had no positive results in human LOAD association studies. These loci were combined with 89 gene loci confirmed as LOAD risk genes in previous GWAS and WES. Of the 313 risk gene loci evaluated, there were 35 human reports on epigenomic modifications in terms of methylation or histone acetylation. 64 microRNA gene regulation mechanisms...
Source: Current Genomics - Category: Genetics & Stem Cells Tags: Curr Genomics Source Type: research

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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, parti...
Source: Fight Aging! - Category: Research Authors: Tags: Daily News Source Type: blogs
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
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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
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Source: The Journal of Lipid Research - Category: Lipidology Authors: Tags: Patient-Oriented and Epidemiological Research Source Type: research
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Source: Fight Aging! - Category: Research Authors: Tags: Newsletters Source Type: blogs
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Source: Trials - Category: Research Source Type: clinical trials
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