scholarly journals Cerebrospinal Fluid of Patients With Alzheimer’s Disease Contains Increased Percentages of Synaptophysin-Bearing Microvesicles

2021 ◽  
Vol 13 ◽  
Author(s):  
Janine Utz ◽  
Judith Berner ◽  
Luis Enrique Muñoz ◽  
Timo Jan Oberstein ◽  
Johannes Kornhuber ◽  
...  
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Cerebrospinal Fluid ◽  
Neurological Disease ◽  
Synaptic Density ◽  
Disease Modifying Drugs ◽  
Future Studies ◽  
Cells Of Origin ◽  
Disease Modifying ◽  
Stressed Cells

IntroductionIn Alzheimer’s disease, the severity of symptoms is linked to a loss of synaptic density and the spread of pathologically hyperphosphorylated tau. The established cerebrospinal fluid markers Aβ, tau and phospho-tau reflect the histopathological hallmarks of Alzheimer’s disease but do not indicate disease progression. Such markers are of special interest, especially for trials of disease modifying drugs. Microvesicles are produced by stressed cells and reflect part of the metabolism of their cells of origin. Therefore, we investigated microvesicles of neuronal origin in cerebrospinal fluid.Materials and MethodsWe used flow cytometry to analyze microvesicles carrying tau, phospho-tau-Thr181, phospho-tau-Ser202Thr205, synaptophysin, and SNAP-25 in the cerebrospinal fluid of 19 patients with Alzheimer’s disease and 15 non-inflammatory neurological disease controls.ResultsThe percentages of synaptophysin-bearing microvesicles were significantly higher in the cerebrospinal fluid of patients with Alzheimer’s disease than in the CSF of non-inflammatory neurological disease controls. Tau, phospho-tau-Thr181, phospho-tau-Ser202Thr205, and SNAP-25 did not differ between the groups. The percentages of synaptophysin-bearing vesicles distinguished patients with Alzheimer’s disease from the controls (AUC = 0.81).ConclusionThe loss of synapses in Alzheimer’s disease may be reflected by synaptophysin-bearing microvesicles in the cerebrospinal fluid. Future studies are needed to investigate the possibility of using these MVs as a marker to determine the activity of Alzheimer’s disease.

scholarly journals Regulatory and Health Technology Assessment Considerations for Disease-Modifying Drugs in Alzheimer’s Disease

CNS Drugs ◽  
2018 ◽  
Vol 32 (12) ◽  
pp. 1085-1090 ◽  
Author(s):  
Jacoline C. Bouvy ◽  
Pall Jonsson ◽  
Diana O’Rourke ◽  
Antonella Santuccione Chadha ◽  
Niklas Hedberg ◽  
...  
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Health Technology Assessment ◽  
Technology Assessment ◽  
Health Technology ◽  
Disease Modifying Drugs ◽  
Disease Modifying

scholarly journals Alzheimer’s Disease: Current and Future Treatments. A Review

2014 ◽  
Vol 2 (2) ◽  
pp. 56-63
Author(s):  
Evelyn Chou
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Cholinesterase Inhibitors ◽  
Neurodegenerative Disorder ◽  
Nmda Antagonists ◽  
Disease Modifying Drugs ◽  
Plaque Deposition ◽  
The Future ◽  
Disease Modifying ◽  
Future Treatments

Alzheimer’s disease (AD) is a currently incurable neurodegenerative disorder whose treatment poses a big challenge. Proposed causes of AD include the cholinergic, amyloid and tau hypotheses. Current therapeutic treatments have been aimed at dealing with the neurotransmitter imbalance. These include cholinesterase inhibitors and N-Methyl-D-aspartate (NMDA) antagonists. However, current therapeutics have been unable to halt AD progression. Much research has gone into the development of disease-modifying drugs to interfere with the course of the disease. Approaches include secretase inhibition and immunotherapy aimed at reducing plaque deposition. However, these have not been successful in curing AD as yet. It is believed that the main reason why therapeutics have failed to work is that treatment begins too late in the course of the disease. The future of AD treatment thus appears to lie with prevention rather than cure. In this article, current therapeutics and, from there, the future of AD treatment are discussed.

Non-cognitive outcomes in trials of disease-modifying drugs for Alzheimer's disease

2012 ◽  
Vol 3 (1) ◽  
pp. 37-42 ◽  
Author(s):  
D. Zekry ◽  
C.E. Graf ◽  
S.V. Giannelli ◽  
G. Gold ◽  
J.-P. Michel
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Cognitive Outcomes ◽  
Disease Modifying Drugs ◽  
Disease Modifying

scholarly journals Cerebrospinal Fluid Biomarkers for Alzheimer’s Disease in the Era of Disease-Modifying Treatments

2021 ◽  
Vol 11 (10) ◽  
pp. 1258
Author(s):  
George P. Paraskevas ◽  
Elisabeth Kapaki
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Cerebrospinal Fluid ◽  
Small Vessel Disease ◽  
Lewy Bodies ◽  
Plaque Burden ◽  
Csf Biomarkers ◽  
Β Amyloid ◽  
Disease Modifying

Correct in vivo diagnosis of Alzheimer’s disease (AD) helps to avoid administration of disease-modifying treatments in non-AD patients, and allows the possible use of such treatments in clinically atypical AD patients. Cerebrospinal fluid (CSF) biomarkers offer a tool for AD diagnosis. A reduction in CSF β-amyloid (marker of amyloid plaque burden), although compatible with Alzheimer’s pathological change, may also be observed in other dementing disorders, including vascular cognitive disorders due to subcortical small-vessel disease, dementia with Lewy bodies and normal-pressure hydrocephalus. Thus, for the diagnosis of AD, an abnormal result of CSF β-amyloid may not be sufficient, and an increase in phospho-tau (marker of tangle pathology) is also required in order to confirm AD diagnosis in patients with a typical amnestic presentation and reveal underlying AD in patients with atypical or mixed and diagnostically confusing clinical presentations.

scholarly journals New Approacher in the Development of Alzheimer’s Disease Modifying Drugs

2021 ◽  
pp. 88
Author(s):  
◽  
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Clinical Trials ◽  
Tau Protein ◽  
Phase Iii ◽  
Disease Modifying Drugs ◽  
Phase Iii Clinical Trials ◽  
Research Level ◽  
Disease Modifying ◽  
Pathological Stages

Introduction: Alzheimer’s disease is a more common neurodegenerative disease, affecting 25 million people worldwide, or accounting for about 60 to 70% of all dementia cases. There is currently no exact mechanism to explain the pathophysiology of Alzheimer’s disease, however, cascading metabolic amyloid and post-translational review of tau protein are used as major hypotheses. Objective: To demonstrate in the literature new approaches in the development of Alzheimer’s disease modifiers. Methodology: For the accomplishment of this study made in the bibliographical survey of scientific literature and respect to the approached subject, in the databases PUBMED, ScienceDirect, Scielo and Scopus. Results: Alzheimer’s disease-modifying drugs are not yet available, but many patients may, however, develop phase III clinical trials and are intended to modify as pathological stages leading to the disease. As disease-modifying therapies under study, these changes also affect Aβ and tau protein and also cause inflammation and oxidative damage. The results obtained in the clinical trials performed were positive and promising and are still under study. The results show that there is still a long way to go in the development of Alzheimer’s disease modifying drugs. Conclusion: The results demonstrated that there is still a long way to go in the development of Alzheimer’s disease modifying drugs, but nevertheless levels at the research level should be continued in order to improve the pathophysiology of the disease and find an effective treatment for this disease the same.

scholarly journals Cerebrospinal fluid and brain PET measures of synaptic density glycoprotein 2A: Biomarkers of synaptic density in Alzheimer’s disease

2021 ◽  
Vol 17 (S5) ◽  
Author(s):  
Adam P. Mecca ◽  
Nicholas J. Ashton ◽  
Ming‐Kai Chen ◽  
Ryan S. O'Dell ◽  
Mika Naganawa ◽  
...  
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Cerebrospinal Fluid ◽  
Synaptic Density ◽  
Brain Pet
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