scholarly journals Site-Specific Cerebrospinal Fluid Tau Hyperphosphorylation in Response to Alzheimer’s Disease Brain Pathology: Not All Tau Phospho-Sites are Hyperphosphorylated

2021 ◽  
pp. 1-15
Author(s):  
Nicolas R. Barthélemy ◽  
Balazs Toth ◽  
Paul T. Manser ◽  
Sandra Sanabria-Bohórquez ◽  
Edmond Teng ◽  
...  
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Tau Phosphorylation ◽  
Amyloid Pet ◽  
Tau Hyperphosphorylation ◽  
Cross Sectional ◽  
Site Specific ◽  
Treatment Objective ◽  
Sectional Analysis ◽  
The Relationship

Background: Understanding patterns of association between CSF phosphorylated tau (p-tau) species and clinical disease severity will aid Alzheimer’s disease (AD) diagnosis and treatment. Objective: To evaluate changes in tau phosphorylation ratios to brain imaging (amyloid PET, [18F]GTP1 PET, and MRI) and cognition across clinical stages of AD in two different cohorts. Methods: A mass spectrometry (MS)-based method was used to evaluate the relationship between p-tau/tau phosphorylation ratios on 11 sites in CSF and AD pathology measured by tau PET ([18F]GTP1) and amyloid PET ([18F]florbetapir or [18F]florbetaben). Cohort A included cognitively normal-amyloid negative (n = 6) and positive (n = 5) individuals, and amyloid positive prodromal (n = 13), mild (n = 12), and moderate AD patients (n = 10); and Cohort B included amyloid positive prodromal (n = 24) and mild (n = 40) AD patients. Results: In this cross-sectional analysis, we identified clusters of phosphosites with different profiles of phosphorylation ratios across stages of disease. Eight of 11 investigated sites were hyperphosphorylated and associated with the SUVR measures from [18F]GTP1 and amyloid PET. Novel sites 111, 153, and 208 may be relevant biomarkers for AD diagnosis to complement tau hyperphosphorylation measures on previously established sites 181, 205, 217, and 231. Hypophosphorylation was detected on residues 175, 199, and 202, and was inversely associated with [18F]GTP1 and amyloid PET. Conclusion: Hyperphosphorylated and hypophosphorylated forms of tau are associated with AD pathologies, and due to their different site-specific profiles, they may be used in combination to assist with staging of disease.

Social support as a mediator variable of the relationship between depression and life satisfaction in a sample of Saudi caregivers of patients with Alzheimer's disease

2016 ◽  
Vol 29 (2) ◽  
pp. 239-248 ◽  
Author(s):  
Shatha Jamil Khusaifan ◽  
Mogeda El Sayed El Keshky
Keyword(s):  
Social Support ◽  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Life Satisfaction ◽  
Cross Sectional Study ◽  
Moderator Variable ◽  
Cross Sectional ◽  
Informal Social Support ◽  
The Relationship ◽  
Mediator Variable

ABSTRACTBackground:Caring for someone with Alzheimer's disease (AD) is very challenging. Social support may play a crucial role in helping caregivers to adapt better to their caregiving role. The aim of this study is to explore the role of social support as a moderator variable of the relationship between depression and life satisfaction in caregivers for patients with AD in Saudi Arabia.Methods:In this cross-sectional study, 122 caregivers for patients with AD completed questionnaires assessing informal social support, depressive symptoms, and general life satisfaction.Results:The demographic characteristics showed that 79% (n = 96) of caregivers were females and between the ages of 20 and 50. Higher levels of social support positively correlated with reported higher levels of life satisfaction (r = 0.483, p < 0.001). Depression was negatively correlated with social support (r = −0.418, p < 0.001) and life satisfaction scores (r = −0.553, p = < 0.001). Social support was found to be a partial mediator variable, mediating approximately 23.05% of the total effect of depression on life satisfaction (Sobel = −3.065, p = 0.002).Conclusion:Informal social support can act as a mediator variable in the relationship of depression and life satisfaction in caregivers of AD patients. Improving the informal social support networks may help in coping with caregiving burden and better quality of life.

scholarly journals Plasma Aβ ratios in autosomal dominant Alzheimer’s disease: the influence of genotype

2021 ◽  
Author(s):  
Antoinette O’Connor ◽  
Josef Pannee ◽  
Teresa Poole ◽  
Charles Arber ◽  
Erik Portelius ◽  
...  
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Autosomal Dominant ◽  
Age At Onset ◽  
Cross Sectional ◽  
Autosomal Dominant Alzheimer’S Disease ◽  
Liquid Chromatography Tandem Mass ◽  
The Relationship

AbstractIn-vitro studies of autosomal dominant Alzheimer’s disease (ADAD) implicate longer Aβ peptides in pathogenesis, however less is known about the behaviour of ADAD mutations in-vivo. In this cross-sectional cohort study, we used liquid chromatography-tandem mass spectrometry to analyse 66 plasma samples from ADAD family members who were at-risk of inheriting a mutation or were already symptomatic. We tested for differences in plasma Aβ42:38, 38:40 and 42:40 ratios between Presenilin1 (PSEN1) and Amyloid Precursor Protein (APP) carriers. We examined the relationship between plasma and in-vitro models of Aβ processing and, among PSEN1 carriers, tested for associations with parental age at onset (AAO). 39 participants were mutation carriers (28 PSEN1 and 11 APP). Age- and sex-adjusted models showed marked differences in plasma Aβ between APP and PSEN1: higher Aβ42:38 in PSEN1 versus APP (p<0.001) and non-carriers (p<0.001); higher Aβ38:40 in APP versus PSEN1 (p<0.001) and non-carriers (p<0.001), while Aβ42:40 was higher in APP and PSEN1 compared to non-carriers (both p<0.001). Aβ profiles were reasonably consistent in plasma and cell lines. Within PSEN1, sex-adjusted models demonstrated negative associations between (i)Aβ42:40 (ii)Aβ42:38 and parental AAO. In-vivo differences in Aβ processing between APP and PSEN1 provide insights into ADAD pathophysiology which can inform therapy development.

scholarly journals SOCIAL COGNITION AND AWARENESS IN ALZHEIMER’S DISEASE

2019 ◽  
Vol 3 (Supplement_1) ◽  
pp. S120-S120
Author(s):  
Marcia Dourado ◽  
Tatiana Belfort ◽  
José Simões Neto
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Social Cognition ◽  
Social Functioning ◽  
Neuropsychiatric Symptoms ◽  
Consecutive Series ◽  
Cross Sectional ◽  
Significant Difference ◽  
Impaired Awareness ◽  
The Relationship

Abstract Social cognition is the capacity to interpret and predict another’s behavior according to beliefs, intentions, and emotions, and the ability to decode environmental stimuli in order to be better able to adapt to new situations. A key question is the relationship between social cognition and awareness in dementia. This study aimed to investigate the relation between social and emotional functioning (SEF) and awareness in Alzheimer's disease (AD). In a cross-sectional design, a consecutive series of 50 people with mild to moderate AD and their 50 family caregivers were assessed. The study variables were awareness, SEF, neuropsychiatric symptoms, cognition, working memory, quality of life, functional activities, presence of depressive symptoms, and caregivers’ burden and cognition. We found a significant difference between self-rated SEF and informant-rated SEF. In 56% of the cases, self-rated SEF was lower than the informant-rated SEF. People with AD mostly (56%) had mildly impaired awareness of disease, 20% had moderate impaired awareness of disease, and 6% were unaware of the disease. A multivariate linear regression examined the association between informant-rated SEF score and the variables. The social functioning and relationship domain of awareness and informant-rated QoL of people with AD were significantly associated with informant-rated SEF. Conclusion: The relationship between informant-rated SEF and awareness of social functioning and relationship supports the multidimensional nature of awareness. SEF and awareness of social functioning shows that they are comprised of judgments related to perceptions about oneself and values qualitatively different from awareness of memory or functionality, which can be directly observed.

Elevated Tau PET Signal Depends on Abnormal Amyloid Levels and Correlates with Cognitive Impairment in Elderly Persons without Dementia

2020 ◽  
Vol 78 (1) ◽  
pp. 395-404 ◽  
Author(s):  
Rui-Qi Zhang ◽  
Shi-Dong Chen ◽  
Xue-Ning Shen ◽  
Yu-Xiang Yang ◽  
Jia-Ying Lu ◽  
...  
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Executive Function ◽  
Amyloid Β ◽  
Amyloid Pet ◽  
Elderly Persons ◽  
Cross Sectional ◽  
Memory Decline ◽  
Tau Pet

Background: The recent developed PET ligands for amyloid-β (Aβ) and tau allow these two neuropathological hallmarks of Alzheimer’s disease (AD) to be mapped and quantified in vivo and to be examined in relation to cognition. Objective: To assess the associations among Aβ, tau, and cognition in non-demented subjects. Methods: Three hundred eighty-nine elderly participants without dementia from the Alzheimer’s Disease Neuroimaging Initiative underwent tau and amyloid PET scans. Cross-sectional comparisons and longitudinal analyses were used to evaluate the relationship between Aβ and tau accumulation. The correlations between biomarkers of both pathologies and performance in memory and executive function were measured. Results: Increased amyloid-PET retention was associated with greater tau-PET retention in widespread cortices. We observed a significant tau increase in the temporal composite regions of interest over 24 months in Aβ+ but not Aβ– subjects. Finally, tau-PET retention but not amyloid-PET retention significantly explained the variance in memory and executive function. Higher level of tau was associated with greater longitudinal memory decline. Conclusion: These findings suggested PET-detectable Aβ plaque pathology may be a necessary antecedent for tau-PET signal elevation. Greater tau-PET retention may demonstrate poorer cognition and predict prospective memory decline in non-demented subjects.

scholarly journals Epigenetic Modulation on Tau Phosphorylation in Alzheimer’s Disease

2019 ◽  
Vol 2019 ◽  
pp. 1-12 ◽  
Author(s):  
Chao-Chao Yu ◽  
Tao Jiang ◽  
Ao-Fei Yang ◽  
Yan-Jun Du ◽  
Miao Wu ◽  
...  
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Noncoding Rna ◽  
Pathological Change ◽  
Epigenetic Modification ◽  
Tau Phosphorylation ◽  
Research Progress ◽  
Tau Hyperphosphorylation ◽  
Rna Regulation ◽  
Epigenetic Modulation

Tau hyperphosphorylation is a typical pathological change in Alzheimer’s disease (AD) and is involved in the early onset and progression of AD. Epigenetic modification refers to heritable alterations in gene expression that are not caused by direct changes in the DNA sequence of the gene. Epigenetic modifications, such as noncoding RNA regulation, DNA methylation, and histone modification, can directly or indirectly affect the regulation of tau phosphorylation, thereby participating in AD development and progression. This review summarizes the current research progress on the mechanisms of epigenetic modification associated with tau phosphorylation.

P-042: Preliminary cross-sectional analysis of pet data from the Alzheimer's disease neuroimaging initiative using morphometry birn procedures

2007 ◽  
Vol 3 (3S_Part_1) ◽  
pp. S110-S110
Author(s):  
David S. Karow ◽  
Donald J. Hagler ◽  
Christine Fennema-Notestine ◽  
Linda K. McEvoy ◽  
Elaine H. Wu ◽  
...  
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Cross Sectional ◽  
Cross Sectional Analysis ◽  
Sectional Analysis
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