Inverse association of cortisol serum levels with T-tau, P-tau 181 and P-tau 231 peptide levels and T-tau/Aβ 1–42 ratios in CSF in patients with mild Alzheimer’s disease dementia

2008 ◽  
Vol 259 (2) ◽  
pp. 80-85 ◽  
Author(s):  
Christoph Laske ◽  
Elke Stransky ◽  
Andreas Fritsche ◽  
Gerhard W. Eschweiler ◽  
Thomas Leyhe
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Serum Levels ◽  
Inverse Association ◽  
T Tau ◽  
Alzheimer’S Disease Dementia

scholarly journals Hearing Loss in Alzheimer’s Disease Is Associated with Altered Serum Lipidomic Biomarker Profiles

Cells ◽  
2020 ◽  
Vol 9 (12) ◽  
pp. 2556
Author(s):  
Daniel Llano ◽  
Lina Issa ◽  
Priya Devanarayan ◽  
Viswanath Devanarayan ◽  
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Hearing Loss ◽  
Antioxidant Properties ◽  
Normal Subjects ◽  
Serum Levels ◽  
Pathological State ◽  
Inverse Association ◽  
Strong Inverse Association ◽  
Potential Factors

Recent data have found that aging-related hearing loss (ARHL) is associated with the development of Alzheimer’s Disease (AD). However, the nature of the relationship between these two disorders is not clear. There are multiple potential factors that link ARHL and AD, and previous investigators have speculated that shared metabolic dysregulation may underlie the propensity to develop both disorders. Here, we investigate the distribution of serum lipidomic biomarkers in AD subjects with or without hearing loss in a publicly available dataset. Serum levels of 349 known lipids from 16 lipid classes were measured in 185 AD patients. Using previously defined co-regulated sets of lipids, both age- and sex-adjusted, we found that lipid sets enriched in phosphatidylcholine and phosphatidylethanolamine showed a strong inverse association with hearing loss. Examination of biochemical classes confirmed these relationships and revealed that serum phosphatidylcholine levels were significantly lower in AD subjects with hearing loss. A similar relationship was not found in normal subjects. These data suggest that a synergistic relationship may exist between AD, hearing loss and metabolic biomarkers, such that in the context of a pathological state such as AD, alterations in serum metabolic profiles are associated with hearing loss. These data also point to a potential role for phosphatidylcholine, a molecule with antioxidant properties, in the underlying pathophysiology of ARHL in the context of AD, which has implications for our understanding and potential treatment of both disorders.

scholarly journals Altered Bile Acid Profile in Mild Cognitive Impairment and Alzheimer’s Disease: Relationship to Neuroimaging and CSF Biomarkers

2018 ◽  
Author(s):  
Kwangsik Nho ◽  
Alexandra Kueider-Paisley ◽  
Siamak MahmoudianDehkordi ◽  
Matthias Arnold ◽  
Shannon L. Risacher ◽  
...  
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Glucose Metabolism ◽  
Cholesterol Metabolism ◽  
Amyloid Β ◽  
Serum Levels ◽  
Model Systems ◽  
Csf Biomarkers ◽  
Clinical Observations ◽  
T Tau

AbstractIntroductionBile acids (BAs) are the end products of cholesterol metabolism produced by human and gut microbiome co-metabolism. Recent evidence suggests gut microbiota influence pathological features of Alzheimer’s disease (AD) including neuroinflammation and amyloid-β deposition.MethodSerum levels of 20 primary and secondary BA metabolites from the AD Neuroimaging Initiative (n=1562) were measured using targeted metabolomic profiling. We assessed the association of BAs with the “A/T/N” (Amyloid, Tau and Neurodegeneration) biomarkers for AD: CSF biomarkers, atrophy (MRI), and brain glucose metabolism ([18F]FDG-PET).ResultsOf 23 BA and relevant calculated ratios, three BA signatures were associated with CSF Aβ1-42 (“A”) and three with CSF p-tau181 (“T”) (corrected p<0.05). Furthermore, three, twelve, and fourteen BA signatures were associated with CSF t-tau, glucose metabolism, and atrophy (“N”), respectively (corrected p<0.05).ConclusionThis is the first study to show serum-based BA metabolites are associated with “A/T/N” AD biomarkers, providing further support for a role of BA pathways in AD pathophysiology. Prospective clinical observations and validation in model systems are needed to assess causality and specific mechanisms underlying this association.

Exploring the Role of Aggregated Proteomes in the Pathogenesis of Alzheimer’s Disease

2020 ◽  
Vol 21 (12) ◽  
pp. 1164-1173
Author(s):  
Siju Ellickal Narayanan ◽  
Nikhila Sekhar ◽  
Rajalakshmi Ganesan Rajamma ◽  
Akash Marathakam ◽  
Abdullah Al Mamun ◽  
...  
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Amyloid Precursor Protein ◽  
Early Onset ◽  
Late Onset ◽  
Precursor Protein ◽  
Brain Disorder ◽  
Amyloid Aβ ◽  
T Tau

: Alzheimer’s disease (AD) is a progressive brain disorder and one of the most common causes of dementia and death. AD can be of two types; early-onset and late-onset, where late-onset AD occurs sporadically while early-onset AD results from a mutation in any of the three genes that include amyloid precursor protein (APP), presenilin 1 (PSEN 1) and presenilin 2 (PSEN 2). Biologically, AD is defined by the presence of the distinct neuropathological profile that consists of the extracellular β-amyloid (Aβ) deposition in the form of diffuse neuritic plaques, intraneuronal neurofibrillary tangles (NFTs) and neuropil threads; in dystrophic neuritis, consisting of aggregated hyperphosphorylated tau protein. Elevated levels of (Aβ), total tau (t-tau) and phosphorylated tau (ptau) in cerebrospinal fluid (CSF) have become an important biomarker for the identification of this neurodegenerative disease. The aggregation of Aβ peptide derived from amyloid precursor protein initiates a series of events that involve inflammation, tau hyperphosphorylation and its deposition, in addition to synaptic dysfunction and neurodegeneration, ultimately resulting in dementia. The current review focuses on the role of proteomes in the pathogenesis of AD.

Pharmacogenetics of Angiotensin-Converting Enzyme Inhibitors in Patients with Alzheimer's Disease Dementia

2018 ◽  
Vol 15 (4) ◽  
pp. 386-398 ◽  
Author(s):  
Fabricio Ferreira de Oliveira ◽  
Elizabeth Suchi Chen ◽  
Marilia Cardoso Smith ◽  
Paulo Henrique Ferreira Bertolucci
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Angiotensin Converting Enzyme ◽  
Cognitive Decline ◽  
Enzyme Inhibitors ◽  
Late Onset ◽  
Amyloid Β ◽  
Converting Enzyme ◽  
Converting Enzyme Inhibitors ◽  
Alzheimer’S Disease Dementia

Background: While the angiotensin-converting enzyme degrades amyloid-β, angiotensinconverting enzyme inhibitors (ACEis) may slow cognitive decline by way of cholinergic effects, by increasing brain substance P and boosting the activity of neprilysin, and by modulating glucose homeostasis and augmenting the secretion of adipokines to enhance insulin sensitivity in patients with Alzheimer’s disease dementia (AD). We aimed to investigate whether ACE gene polymorphisms rs1800764 and rs4291 are associated with cognitive and functional change in patients with AD, while also taking APOE haplotypes and anti-hypertensive treatment with ACEis into account for stratification. Methods: Consecutive late-onset AD patients were screened with cognitive tests, while their caregivers were queried for functional and caregiver burden scores. Prospective pharmacogenetic correlations were estimated for one year, considering APOE and ACE genotypes and haplotypes, and treatment with ACEis. Results: For 193 patients, minor allele frequencies were 0.497 for rs1800764 – C (44.6% heterozygotes) and 0.345 for rs4291 – T (38.9% heterozygotes), both in Hardy-Weinberg equilibrium. Almost 94% of all patients used cholinesterase inhibitors, while 155 (80.3%) had arterial hypertension, and 124 used ACEis. No functional impacts were found regarding any genotypes or pharmacological treatment. Either for carriers of ACE haplotypes that included rs1800764 – T and rs4291 – A, or for APOE4- carriers of rs1800764 – T or rs4291 – T, ACEis slowed cognitive decline independently of blood pressure variations. APOE4+ carriers were not responsive to treatment with ACEis. Conclusion: ACEis may slow cognitive decline for patients with AD, more remarkably for APOE4- carriers of specific ACE genotypes.

scholarly journals Prediction of future Alzheimer’s disease dementia using plasma phospho-tau combined with other accessible measures

2021 ◽  
Author(s):  
Sebastian Palmqvist ◽  
◽  
Pontus Tideman ◽  
Nicholas Cullen ◽  
Henrik Zetterberg ◽  
...  
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Alzheimer’S Disease Dementia

scholarly journals Association between methylation of BIN1 promoter in peripheral blood and preclinical Alzheimer’s disease

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Hao Hu ◽  
Lan Tan ◽  
Yan-Lin Bi ◽  
Wei Xu ◽  
Lin Tan ◽  
...  
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Peripheral Blood ◽  
Late Onset ◽  
Early Stage ◽  
Susceptibility Gene ◽  
Subjective Cognitive Decline ◽  
Preclinical Ad ◽  
T Tau ◽  
New Evidence

AbstractThe bridging integrator 1 (BIN1) gene is the second most important susceptibility gene for late-onset Alzheimer’s disease (LOAD) after apolipoprotein E (APOE) gene. To explore whether the BIN1 methylation in peripheral blood changed in the early stage of LOAD, we included 814 participants (484 cognitively normal participants [CN] and 330 participants with subjective cognitive decline [SCD]) from the Chinese Alzheimer’s Biomarker and LifestylE (CABLE) database. Then we tested associations of methylation of BIN1 promoter in peripheral blood with the susceptibility for preclinical AD or early changes of cerebrospinal fluid (CSF) AD-related biomarkers. Results showed that SCD participants with significant AD biological characteristics had lower methylation levels of BIN1 promoter, even after correcting for covariates. Hypomethylation of BIN1 promoter were associated with decreased CSF Aβ42 (p = 0.0008), as well as increased p-tau/Aβ42 (p = 0.0001) and t-tau/Aβ42 (p < 0.0001) in total participants. Subgroup analysis showed that the above associations only remained in the SCD subgroup. In addition, hypomethylation of BIN1 promoter was also accompanied by increased CSF p-tau (p = 0.0028) and t-tau (p = 0.0130) in the SCD subgroup, which was independent of CSF Aβ42. Finally, above associations were still significant after correcting single nucleotide polymorphic sites (SNPs) and interaction of APOE ɛ4 status. Our study is the first to find a robust association between hypomethylation of BIN1 promoter in peripheral blood and preclinical AD. This provides new evidence for the involvement of BIN1 in AD, and may contribute to the discovery of new therapeutic targets for AD.

scholarly journals Brain-Derived Exosomal Proteins as Effective Biomarkers for Alzheimer’s Disease: A Systematic Review and Meta-Analysis

Biomolecules ◽  
2021 ◽  
Vol 11 (7) ◽  
pp. 980
Author(s):  
Ka-Young Kim ◽  
Ki-Young Shin ◽  
Keun-A. Chang
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Web Of Science ◽  
Meta Analysis ◽  
Cochrane Library ◽  
Blood Biomarkers ◽  
Cell Lineages ◽  
The Central Nervous System ◽  
New Biomarkers ◽  
T Tau

Alzheimer’s disease (AD), a progressive neurodegenerative disease, affects approximately 50 million people worldwide, which warrants the search for reliable new biomarkers for early diagnosis of AD. Brain-derived exosomal (BDE) proteins, which are extracellular nanovesicles released by all cell lineages of the central nervous system, have been focused as biomarkers for diagnosis, screening, prognosis prediction, and monitoring in AD. This review focused on the possibility of BDE proteins as AD biomarkers. The articles published prior to 26 January 2021 were searched in PubMed, EMBASE, Web of Science, and Cochrane Library to identify all relevant studies that reported exosome biomarkers in blood samples of patients with AD. From 342 articles, 20 studies were selected for analysis. We conducted a meta-analysis of six BDE proteins and found that levels of amyloid-β42 (standardized mean difference (SMD) = 1.534, 95% confidence interval [CI]: 0.595–2.474), total-tau (SMD = 1.224, 95% CI: 0.534–1.915), tau phosphorylated at threonine 181 (SMD = 4.038, 95% CI: 2.312-5.764), and tau phosphorylated at serine 396 (SMD = 2.511, 95% CI: 0.795–4.227) were significantly different in patients with AD compared to those in control. Whereas, those of p-tyrosine-insulin receptor substrate-1 and heat shock protein 70 did not show significant differences. This review suggested that Aβ42, t-tau, p-T181-tau, and p-S396-tau could be effective in diagnosing AD as blood biomarkers, despite the limitation in the meta-analysis based on the availability of data. Therefore, certain BDE proteins could be used as effective biomarkers for AD.

The Associations of Plasma/Serum Carotenoids with Alzheimer’s Disease: A Systematic Review and Meta-Analysis

2021 ◽  
pp. 1-12
Author(s):  
Mingyue Qu ◽  
Hanxu Shi ◽  
Kai Wang ◽  
Xinggang Wang ◽  
Nan Yu ◽  
...  
Keyword(s):  
Systematic Review ◽  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Meta Analysis ◽  
Scoring Systems ◽  
Serum Levels ◽  
Epidemiological Studies ◽  
Pooled Analysis ◽  
Protective Effects ◽  
Mean Differences

Background: Multiple lines of evidence indicate protective effects of carotenoids in Alzheimer’s disease (AD). However, previous epidemiological studies reported inconsistent results regarding the associations between carotenoids levels and the risk of AD. Objective: Our study aims to evaluate the associations of six major members of carotenoids with the occurrence of AD by conducting a systematic review and meta-analysis. Methods: Following PRISMA guidelines, a comprehensive literature search of PubMed, Web of Science, Ebsco, and PsycINFO databases was conducted, and the quality of each included studies was evaluated by a validated scoring systems. Standardized mean differences (SMD) with 95%confidence intervals (CI) were determined by using a random effects model. Heterogeneity was evaluated by I2 statistics. Publication bias was detected using funnel plots and Egger’s test. Results: Sixteen studies, with 10,633 participants were included. Pooled analysis showed significantly lower plasma/serum levels of lutein (SMD = –0.86, 95%CI: –1.67 to –0.05, p = 0.04) and zeaxanthin (SMD = –0.59; 95%CI: –1.12 to –0.06, p = 0.03) in patients with AD versus cognitively intact controls, while α-carotene (SMD = 0.21, 95%CI: –0.68 to 0.26, p = 0.39), β-carotene (SMD = 0.04, 95%CI: –0.57 to 0.65, p = 0.9), lycopene (SMD = –0.12, 95%CI: –0.96 to 0.72, p = 0.78), and β-cryptoxanthin (SMD = –0.09, 95%CI: –0.83 to 0.65, p = 0.81) did not achieve significant differences. Conclusion: Of six major members of carotenoids, only lutein and zeaxanthin concentrations in plasma/serum were inversely related to the risk of AD. More high-quality longitudinal studies are needed to verify these findings.

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