Interactive effect of age and APOE-ε4 allele load on white matter myelin content in cognitively normal middle-aged subjects

We examined T1w/T2w ratio maps in 515 cognitively healthy middle-aged participants from the ALFA study (ALzheimer and FAmilies) cohort, a single-site population-based study enriched for AD risk (68 APOE-ε4 homozygotes, 197 heterozygotes, and 250 non-carriers). Using tract-based spatial statistics, we assessed the impact of age and APOE genotype on this ratio taken as an indirect descriptor of myelin content.Healthy APOE-ε4 carriers display decreased T1w/T2w ratios in extensive regions in a dose-dependent manner. These differences were found to interact with age, suggesting faster changes in individuals with more ε4 alleles.These results obtained with T1w/T2w ratios, confirm the increased vulnerability of WM tracts in APOE-ε4 healthy carriers. Early alterations of myelin content could be the result of the impaired function of the ε4 isoform of the APOE protein in cholesterol transport. These findings help to clarify the possible interactions between the APOE-dependent non-pathological burden and age-related changes potentially at the source of the AD pathological cascade.
Source: NeuroImage: Clinical - Category: Radiology Source Type: research

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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
Here Matthew O'Connor of the SENS Research Foundation talks about the research that led to founding of Underdog Pharmaceuticals, a biotech startup incubated by the foundation to commercialize a means of targeting 7-ketocholesterol in atherosclerosis and other conditions. Oxidized cholesterols, and largely 7-ketocholesterol, are the primary cause of dysfunction in the macrophage cells normally responsible for preventing the build up of fatty plaques in blood vessel walls. That dysfunction is the cause of atherosclerosis, and the fact that the presence of oxidized cholesterols increases with age is one of the reasons why ath...
Source: Fight Aging! - Category: Research Authors: Tags: Healthy Life Extension Community Source Type: blogs
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
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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
CONCLUSION: Although there are several lines of evidence from cell-based and animal studies that suggest that ACAT inhibition is an effective way of reducing cerebral Aβ, there is still an information gap in terms of mechanisms and concerns to cover before passing to the next level. Additionally, an area of interest that may be useful in understanding AD to subsequently propose new therapeutic approaches is pharmacogenetics; however, there is still a lot of missing information in this area. PMID: 31441726 [PubMed - as supplied by publisher]
Source: Current Alzheimer Research - Category: Neurology Authors: Tags: Curr Alzheimer Res Source Type: research
We examined 9293 individuals from the Copenhagen General Population Study using nuclear magnetic resonance spectroscopy measurements of total cholesterol, free- and esterified cholesterol, triglycerides, phospholipids, and particle concentration. Fourteen subclasses of decreasing size and their lipid constituents were analysed: six subclasses were very low-density lipoprotein (VLDL), one intermediate-density lipoprotein (IDL), three low-density lipoprotein (LDL), and four subclasses were high-density lipoprotein (HDL). Remnant lipoproteins were VLDL and IDL combined. Mean nonfasting cholesterol concentration was 72...
Source: Fight Aging! - Category: Research Authors: Tags: Newsletters Source Type: blogs
Formononetin ameliorates cognitive disorder via PGC-1α pathway in neuroinflammation conditions in high-fat diet-induced mice. CNS Neurol Disord Drug Targets. 2019 Aug 07;: Authors: Fu X, Qin T, Yu J, Jiao J, Ma Z, Fu Q, Deng X, Ma S Abstract Alzheimer's disease (AD) is one of the most common neurodegenerative diseases in many modern societies. Previous studies have shown that neuroinflammation is one of the pathogenesis of AD. Formononetin (FN), an isoflavone compound extracted from Trifolium pratense L., has been found to have various properties including anti-obesity, anti-inflammation, and ne...
Source: CNS and Neurological Disorders Drug Targets - Category: Drugs & Pharmacology Authors: Tags: CNS Neurol Disord Drug Targets Source Type: research
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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