Hyperconnectivity of Self-Referential Network as a Predictive Biomarker of the Progression of Alzheimer’s Disease

2021 ◽  
Vol 80 (2) ◽  
pp. 577-590
Author(s):  
Weina Yao ◽  
Haifeng Chen ◽  
Caimei Luo ◽  
Xiaoning Sheng ◽  
Hui Zhao ◽  
...  

Background: Self-referential processing is associated with the progression of Alzheimer’s disease (AD), and cerebrospinal fluid (CSF) proteins have become accepted biomarkers of AD. Objective: Our objective in this study was to focus on the relationships between the self-referential network (SRN) and CSF pathology in AD-spectrum patients. Methods: A total of 80 participants, including 20 cognitively normal, 20 early mild cognitive impairment (EMCI), 20 late MCI (LMCI), and 20 AD, were recruited for this study. Independent component analysis was used to explore the topological SRN patterns, and the abnormalities of this network were identified at different stages of AD. Finally, CSF pathological characteristics (i.e., CSF Aβ, t-tau, and p-tau) that affected the abnormalities of the SRN were further determined during the progression of AD. Results: Compared to cognitively normal subjects, AD-spectrum patients (i.e., EMCI, LMCI, and AD) showed a reversing trend toward an association between CSF pathological markers and the abnormal SRN occurring during the progression of AD. However, a certain disease state (i.e., the present LMCI) with a low concentration of CSF tau could evoke more hyperconnectivity of the SRN than other patients with progressively increasing concentrations of CSF tau (i.e., EMCI and AD), and this fluctuation of CSF tau was more sensitive to the hyperconnectivity of the SRN than the dynamic changes of CSF Aβ. Conclusion: The integrity of the SRN was closely associated with CSF pathological characteristics, and these findings support the view that the hyperconnectivity of the SRN will play an important role in monitoring the progression of the pre-dementia state to AD.

2021 ◽  
Vol 12 ◽  
Author(s):  
Karolina Wilczyńska ◽  
Mateusz Maciejczyk ◽  
Anna Zalewska ◽  
Napoleon Waszkiewicz

Introduction: The diagnosis and treatment of dementia is one of the greatest challenges in contemporary health care. The widespread use of dementia biomarkers would improve the quality of life of patients and reduce the economic costs of the disease. The aim of the study was to evaluate the usefulness of proteins related to the Alzheimer's disease pathogenesis—amyloid beta isoform (Aβ) and total tau protein (t-tau), as well as the quite recently discovered marker YKL-40 in the most common types of dementia.Methods: 60 dementia (AD—Alzheimer's disease, VaD—vascular dementia, MxD—mixed dementia) and 20 cognitively normal subjects over 60 years old were examined. Subjects with dementia of etiology different than AD or VaD and with neoplastic or chronic inflammatory diseases were excluded. Concentrations of Aβ40, Aβ42, t-tau, and YKL-40 were measured in serum using ELISA kits on admission and after 4 weeks of inpatient treatment. ANOVA and Tukey's test or Dunn's test were used to perform comparison tests between groups. Correlations were measured using Pearson's coefficient. Biomarker diagnostic utility was assessed with ROC analysis.Results: YKL-40 differentiates between cognitively normal and mild dementia patients with 85% sensitivity and specificity and t-tau with 72% sensitivity and 70% specificity. YKL-40 and t-tau concentrations correlate with each other and with the severity of clinically observed cognitive decline.Conclusions: YKL-40 is a sensitive and specific biomarker of early dementia and, to a lesser extent, of dementia progression, however, many comorbidities may influence its levels. In such conditions, less specific but still reliable t-tau may serve as an alternative marker. Obtained results did not confirm the diagnostic utility of amyloid biomarkers.


Brain ◽  
2015 ◽  
Vol 138 (9) ◽  
pp. 2701-2715 ◽  
Author(s):  
Jon B. Toledo ◽  
Henrik Zetterberg ◽  
Argonde C. van Harten ◽  
Lidia Glodzik ◽  
Pablo Martinez-Lage ◽  
...  

2019 ◽  
Vol 15 ◽  
pp. P384-P385
Author(s):  
Merle C. Hönig ◽  
Gerard N. Bischof ◽  
Isadora Lopes Alves ◽  
Mareike Ahlswede ◽  
Panagiotis Sakagiannis ◽  
...  

2017 ◽  
Vol 13 (7S_Part_6) ◽  
pp. P295-P296
Author(s):  
Shahzad Ahmad ◽  
Christian Bannister ◽  
Sven J. van der Lee ◽  
Dina Vojinovic ◽  
Hieab H.H. Adams ◽  
...  

2013 ◽  
Vol 9 ◽  
pp. P257-P257
Author(s):  
Prashanthi Vemuri ◽  
Heather Wiste ◽  
Stephen Weigand ◽  
David Knopman ◽  
Michelle Mielke ◽  
...  

2021 ◽  
Vol 14 ◽  
Author(s):  
Dong-Yu Fan ◽  
Hao-Lun Sun ◽  
Pu-Yang Sun ◽  
Jie-Ming Jian ◽  
Wei-Wei Li ◽  
...  

Recent studies show that fibrinogen plays a role in the pathogenesis of Alzheimer’s disease (AD), which may be crucial to neurovascular damage and cognitive impairment. However, there are few clinical studies on the relationship between fibrinogen and AD. 59 11C-PiB-PET diagnosed AD patients and 76 age- and gender-matched cognitively normal controls were included to analyze the correlation between plasma β-amyloid (Aβ) and tau levels with fibrinogen levels. 35 AD patients and 76 controls with cerebrospinal fluid (CSF) samples were included to further analyze the correlation between CSF Aβ and tau levels with fibrinogen levels. In AD patients, plasma fibrinogen levels were positively correlated with plasma Aβ40 and Aβ42 levels, and negatively correlated with CSF Aβ42 levels. Besides, fibrinogen levels were positively correlated with CSF total tau (t-tau), and phosphorylated tau-181 (p-tau) levels and positively correlated with the indicators of Aβ deposition in the brain, such as t-tau/Aβ42, p-tau/Aβ42 levels. In normal people, fibrinogen levels lack correlation with Aβ and tau levels in plasma and CSF. This study suggests that plasma fibrinogen levels are positively correlated with Aβ levels in the plasma and brain in AD patients. Fibrinogen may be involved in the pathogenesis of AD.


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