Apolipoprotein A1 in Cerebrospinal Fluid and Plasma and Progression to Alzheimer’s Disease in Non-Demented Elderly

2017 ◽  
Vol 56 (2) ◽  
pp. 687-697 ◽  
Author(s):  
Rosalinde E.R. Slot ◽  
Argonde C. Van Harten ◽  
Maartje I. Kester ◽  
Wesley Jongbloed ◽  
Femke H. Bouwman ◽  
...  
Antioxidants ◽  
2020 ◽  
Vol 9 (5) ◽  
pp. 456 ◽  
Author(s):  
Arianna Romani ◽  
Alessandro Trentini ◽  
Wiesje M. van der Flier ◽  
Tiziana Bellini ◽  
Giovanni Zuliani ◽  
...  

Background: It has been suggested that circulating Paraoxonase-1 (PON1) and apolipoprotein A1 (APOA1), which closely interacts with the antioxidant enzyme, could be implicated in Alzheimer’s disease (AD) and vascular dementia (VaD) development. This study aimed to evaluate PON1 changes in serum and cerebrospinal fluid (CSF) as evidence for its association with AD or VaD. Methods: Serum PON-arylesterase activity was measured in patients with AD, VaD, and CONTROLS distributed in two cohorts: Ferrara cohort (FC: n = 503, age = 74 years) and Amsterdam Dementia cohort (ADC: n = 71, age = 65 years). In the last cohort, CSF PON-arylesterase, CSF β-amyloid1-42, p-tau and t-tau, and imaging biomarkers were also measured. Results: AD and VaD patients of FC showed significantly lower levels of serum PON-arylesterase compared to CONTROLS, but this outcome was driven by older subjects (>71 years, p < 0.0001). In the younger ADC, a similar decreasing (but not significant) trend was observed in serum and CSF. Intriguingly, PON-arylesterase per APOA1 correlated with t-tau in AD group (r = −0.485, p = 0.002). Conclusion: These results suggest that decreased peripheral PON-arylesterase might be a specific feature of older AD/VaD patients. Moreover, we showed that PON-arylesterase/APOA1 is inversely related to neurodegeneration in AD patients, suggesting a prognostic usefulness of this composite parameter.


2020 ◽  
Vol 4 (1) ◽  
pp. 15-19 ◽  
Author(s):  
Nicolai Maximilian Stoye ◽  
Patrick Jung ◽  
Malena dos Santos Guilherme ◽  
Johannes Lotz ◽  
Andreas Fellgiebel ◽  
...  

HAPS Educator ◽  
2015 ◽  
Vol 20 (1) ◽  
pp. 38-43
Author(s):  
Brie Paddock ◽  
Kimberly Canfield ◽  
Sarah Cooper

2021 ◽  
pp. 174077452110344
Author(s):  
Michelle M Nuño ◽  
Joshua D Grill ◽  
Daniel L Gillen ◽  

Background/Aims: The focus of Alzheimer’s disease studies has shifted to earlier disease stages, including mild cognitive impairment. Biomarker inclusion criteria are often incorporated into mild cognitive impairment clinical trials to identify individuals with “prodromal Alzheimer’s disease” to ensure appropriate drug targets and enrich for participants likely to develop Alzheimer’s disease dementia. The use of these eligibility criteria may affect study power. Methods: We investigated outcome variability and study power in the setting of proof-of-concept prodromal Alzheimer’s disease trials that incorporate cerebrospinal fluid levels of total tau (t-tau) and phosphorylated (p-tau) as primary outcomes and how differing biomarker inclusion criteria affect power. We used data from the Alzheimer’s Disease Neuroimaging Initiative to model trial scenarios and to estimate the variance and within-subject correlation of total and phosphorylated tau. These estimates were then used to investigate the differences in study power for trials considering these two surrogate outcomes. Results: Patient characteristics were similar for all eligibility criteria. The lowest outcome variance and highest within-subject correlation were obtained when phosphorylated tau was used as an eligibility criterion, compared to amyloid beta or total tau, regardless of whether total tau or phosphorylated tau were used as primary outcomes. Power increased when eligibility criteria were broadened to allow for enrollment of subjects with either low amyloid beta or high phosphorylated tau. Conclusion: Specific biomarker inclusion criteria may impact statistical power in trials using total tau or phosphorylated tau as the primary outcome. In concert with other important considerations such as treatment target and population of clinical interest, these results may have implications to the integrity and efficiency of prodromal Alzheimer’s disease trial designs.


2021 ◽  
Vol 16 (1) ◽  
Author(s):  
Yuxing Xia ◽  
Stefan Prokop ◽  
Benoit I. Giasson

AbstractPhosphorylation is one of the most prevalent post-translational modifications found in aggregated tau isolated from Alzheimer’s disease (AD) patient brains. In tauopathies like AD, increased phosphorylation or hyperphosphorylation can contribute to microtubule dysfunction and is associated with tau aggregation. In this review, we provide an overview of the structure and functions of tau protein as well as the physiologic roles of tau phosphorylation. We also extensively survey tau phosphorylation sites identified in brain tissue and cerebrospinal fluid from AD patients compared to age-matched healthy controls, which may serve as disease-specific biomarkers. Recently, new assays have been developed to measure minute amounts of specific forms of phosphorylated tau in both cerebrospinal fluid and plasma, which could potentially be useful for aiding clinical diagnosis and monitoring disease progression. Additionally, multiple therapies targeting phosphorylated tau are in various stages of clinical trials including kinase inhibitors, phosphatase activators, and tau immunotherapy. With promising early results, therapies that target phosphorylated tau  could be useful at slowing tau hyperphosphorylation and aggregation in AD and other tauopathies.


2010 ◽  
Vol 23 (2) ◽  
pp. 330-331
Author(s):  
Brendan Silbert ◽  
David Scott ◽  
Lisbeth Evered ◽  
Paul Maruff

The growing need for lumbar puncture in order to obtain cerebrospinal fluid (CSF) for the diagnosis Alzheimer's disease is becoming increasingly apparent (Herskovits and Growdon, 2010). The concept of a CSF sampling unit specializing in lumbar puncture would seem the most plausible solution. Physicians and interns are not necessarily skilled in the procedure and neurologists perform lumbar puncture rarely.


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