scholarly journals Increasing the reproducibility of fluid biomarker studies in neurodegenerative studies

2020 ◽  
Vol 11 (1) ◽  
Author(s):  
Niklas Mattsson-Carlgren ◽  
Sebastian Palmqvist ◽  
Kaj Blennow ◽  
Oskar Hansson
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Neurodegenerative Diseases ◽  
Trial Design ◽  
Patient Management ◽  
Drug Trial ◽  
Journal Editors ◽  
Cerebrospinal Fluid Biomarkers ◽  
Novel Biomarkers ◽  
Fluid Biomarker

AbstractBiomarkers have revolutionized scientific research on neurodegenerative diseases, in particular Alzheimer’s disease, transformed drug trial design, and are also increasingly improving patient management in clinical practice. A few key cerebrospinal fluid biomarkers have been robustly associated with neurodegenerative diseases. Several novel biomarkers are very promising, especially blood-based markers. However, many biomarker findings have had low reproducibility despite initial promising results. In this perspective, we identify possible sources for low reproducibility of studies on fluid biomarkers for neurodegenerative diseases, with a focus on Alzheimer’s disease. We suggest guidelines for researchers and journal editors, with the aim to improve reproducibility of findings.

scholarly journals Comparison of the clinical impact of 2-[18F]FDG-PET and cerebrospinal fluid biomarkers in patients suspected of Alzheimer’s disease

PLoS ONE ◽  
2021 ◽  
Vol 16 (3) ◽  
pp. e0248413
Author(s):  
Le Gjerum ◽  
Birgitte Bo Andersen ◽  
Marie Bruun ◽  
Anja Hviid Simonsen ◽  
Otto Mølby Henriksen ◽  
...  
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Cerebrospinal Fluid ◽  
Fdg Pet ◽  
Patient Management ◽  
Clinical Impact ◽  
Diagnostic Evaluation ◽  
Disease Course ◽  
Clinical Value ◽  
Cerebrospinal Fluid Biomarkers

Background The two biomarkers 2-[18F]FDG-PET and cerebrospinal fluid biomarkers are both recommended to support the diagnosis of Alzheimer’s disease. However, there is a lack of knowledge for the comparison of the two biomarkers in a routine clinical setting. Objective The aim was to compare the clinical impact of 2-[18F]FDG-PET and cerebrospinal fluid biomarkers on diagnosis, prognosis, and patient management in patients suspected of Alzheimer’s disease. Methods Eighty-one patients clinically suspected of Alzheimer’s disease were retrospectively included from the Copenhagen Memory Clinic. As part of the clinical work-up all patients had a standard diagnostic program examination including MRI and ancillary investigations with 2-[18F]FDG-PET and cerebrospinal fluid biomarkers. An incremental study design was used to evaluate the clinical impact of the biomarkers. First, the diagnostic evaluation was based on the standard diagnostic program, then the diagnostic evaluation was revised after addition of either cerebrospinal fluid biomarkers or 2-[18F]FDG-PET. At each diagnostic evaluation, two blinded dementia specialists made a consensus decision on diagnosis, prediction of disease course, and change in patient management. Confidence in the decision was measured on a visual analogue scale (0–100). After 6 months, the diagnostic evaluation was performed with addition of the other biomarker. A clinical follow-up after 12 months was used as reference for diagnosis and disease course. Results The two biomarkers had a similar clinical value across all diagnosis when added individually to the standard diagnostic program. However, for the correctly diagnosed patient with Alzheimer’s disease cerebrospinal fluid biomarkers had a significantly higher impact on diagnostic confidence (mean scores±SD: 88±11 vs. 82±11, p = 0.046) and a significant reduction in the need for ancillary investigations (23 vs. 18 patients, p = 0.049) compared to 2-[18F]FDG-PET. Conclusion The two biomarkers had similar clinical impact on diagnosis, but cerebrospinal fluid biomarkers had a more significant value in corroborating the diagnosis of Alzheimer’s disease compared to 2-[18F]FDG-PET.

scholarly journals DNA Methylation: A Promising Approach in Management of Alzheimer’s Disease and Other Neurodegenerative Disorders

Biology ◽  
2022 ◽  
Vol 11 (1) ◽  
pp. 90
Author(s):  
Gagandeep Kaur ◽  
Suraj Singh S. Rathod ◽  
Mohammed M. Ghoneim ◽  
Sultan Alshehri ◽  
Javed Ahmad ◽  
...  
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Dna Methylation ◽  
Neurodegenerative Diseases ◽  
Epigenetic Modification ◽  
Research Area ◽  
Potential Biomarker ◽  
Novel Biomarkers ◽  
Different Populations

DNA methylation, in the mammalian genome, is an epigenetic modification that involves the transfer of a methyl group on the C5 position of cytosine to derive 5-methylcytosine. The role of DNA methylation in the development of the nervous system and the progression of neurodegenerative diseases such as Alzheimer’s disease has been an interesting research area. Furthermore, mutations altering DNA methylation affect neurodevelopmental functions and may cause the progression of several neurodegenerative diseases. Epigenetic modifications in neurodegenerative diseases are widely studied in different populations to uncover the plausible mechanisms contributing to the development and progression of the disease and detect novel biomarkers for early prognosis and future pharmacotherapeutic targets. In this manuscript, we summarize the association of DNA methylation with the pathogenesis of the most common neurodegenerative diseases, such as, Alzheimer’s disease, Parkinson’s disease, Huntington diseases, and amyotrophic lateral sclerosis, and discuss the potential of DNA methylation as a potential biomarker and therapeutic tool for neurogenerative diseases.

Biomarkers in Alzheimer’s disease

2020 ◽  
Vol 0 (0) ◽  
Author(s):  
Manuel H. Janeiro ◽  
Carlos G. Ardanaz ◽  
Noemí Sola-Sevilla ◽  
Jinya Dong ◽  
María Cortés-Erice ◽  
...  
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Clinical Symptoms ◽  
Biological Fluids ◽  
Pathological Process ◽  
Positron Emission ◽  
Cerebrospinal Fluid Biomarkers ◽  
Novel Biomarkers ◽  
Definition Of ◽  
T Tau

AbstractBackgroundAlzheimer’s disease (AD) is a progressive neurodegenerative disease. AD is the main cause of dementia worldwide and aging is the main risk factor for developing the illness. AD classical diagnostic criteria rely on clinical data. However, the development of a biological definition of AD using biomarkers that reflect the underling neuropathology is needed.ContentThe aim of this review is to describe the main outcomes when measuring classical and novel biomarkers in biological fluids or neuroimaging.SummaryNowadays, there are three classical biomarkers for the diagnosis of AD: Aβ42, t-Tau and p-Tau. The diagnostic use of cerebrospinal fluid biomarkers is limited due to invasive collection by lumbar puncture with potential side effects. Plasma/serum measurements are the gold standard in clinics, because they are minimally invasive and, in consequence, easily collected and processed. The two main proteins implicated in the pathological process, Aβ and Tau, can be visualized using neuroimaging techniques, such as positron emission tomography.OutlookAs it is currently accepted that AD starts decades before clinical symptoms could be diagnosed, the opportunity to detect biological alterations prior to clinical symptoms would allow early diagnosis or even perhaps change treatment possibilities.

scholarly journals Integrated Proteomics Reveals Brain-Based Cerebrospinal Fluid Biomarkers in Asymptomatic and Symptomatic Alzheimer’s Disease

2019 ◽  
Author(s):  
Lenora Higginbotham ◽  
Lingyan Ping ◽  
Eric B. Dammer ◽  
Duc M. Duong ◽  
Maotian Zhou ◽  
...  
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Cerebrospinal Fluid ◽  
Postmortem Brain ◽  
Csf Biomarkers ◽  
Amyloid Accumulation ◽  
Cerebrospinal Fluid Biomarkers ◽  
Novel Biomarkers ◽  
The Brain ◽  
Brain Tissues

AbstractAlzheimer’s disease (AD) features a complex web of pathological processes beyond amyloid accumulation and tau-mediated neuronal death. To meaningfully advance AD therapeutics, there is an urgent need for novel biomarkers that comprehensively reflect these disease mechanisms. Here we applied an integrative proteomics approach to identify cerebrospinal fluid (CSF) biomarkers linked to a diverse set of pathophysiological processes in the diseased brain. Using multiplex proteomics, we identified >3,500 proteins across 40 CSF samples from control and AD patients and >12,000 proteins across 48 postmortem brain tissues from control, asymptomatic AD (AsymAD), AD, and other neurodegenerative cases. Co-expression network analysis of the brain tissues resolved 44 protein modules, nearly half of which significantly correlated with AD neuropathology. Fifteen modules robustly overlapped with proteins quantified in the CSF, including 271 CSF markers highly altered in AD. These 15 overlapping modules were collapsed into five panels of brain-linked fluid markers representing a variety of cortical functions. Neuron-enriched synaptic and metabolic panels demonstrated decreased levels in the AD brain but increased levels in diseased CSF. Conversely, glial-enriched myelination and immunity panels were highly increased in both the brain and CSF. Using high-throughput proteomic analysis, proteins from these panels were validated in an independent CSF cohort of control, AsymAD, and AD samples. Remarkably, several validated markers were significantly altered in AsymAD CSF and appeared to stratify subpopulations within this cohort. Overall, these brain-linked CSF biomarker panels represent a promising step toward a physiologically comprehensive tool that could meaningfully enhance the prognostic and therapeutic management of AD.

Effect Of Nhexane Extract Of Caryota No Seed On Markers Of Neurodegeneration And Fecundity In Drosophila Melanogaster

2020 ◽  
Vol 6 (5) ◽  
pp. 1-7
Author(s):  
Chinonye A Maduagwuna ◽  
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Drosophila Melanogaster ◽  
Neurodegenerative Diseases ◽  
Cognitive Functions ◽  
The Elderly ◽  
Common Cause ◽  
Chronic Neuroinflammation

Study background: Chronic neuroinflammation is a common emerging hallmark of several neurodegenerative diseases. Alzheimer’s Disease (AD) is the most common cause of dementia among the elderly and is characterized by loss of memory and other cognitive functions.

scholarly journals Antia, a Natural Antioxidant Product, Attenuates Cognitive Dysfunction in Streptozotocin-Induced Mouse Model of Sporadic Alzheimer’s Disease by Targeting the Amyloidogenic, Inflammatory, Autophagy, and Oxidative Stress Pathways

2020 ◽  
Vol 2020 ◽  
pp. 1-14
Author(s):  
Nesrine S. El Sayed ◽  
Mamdooh H. Ghoneum
Keyword(s):  
Oxidative Stress ◽  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Neurodegenerative Diseases ◽  
Protective Effect ◽  
Cognitive Dysfunction ◽  
Protective Role ◽  
Sporadic Alzheimer’S Disease ◽  
Stat3 Pathway ◽  
And Oxidative Stress

Background. Many neurodegenerative diseases such as Alzheimer’s disease are associated with oxidative stress. Therefore, antioxidant therapy has been suggested for the prevention and treatment of neurodegenerative diseases. Objective. We investigated the ability of the antioxidant Antia to exert a protective effect against sporadic Alzheimer’s disease (SAD) induced in mice. Antia is a natural product that is extracted from the edible yamabushitake mushroom, the gotsukora and kothala himbutu plants, diosgenin (an extract from wild yam tubers), and amla (Indian gooseberry) after treatment with MRN-100. Methods. Single intracerebroventricular (ICV) injection of streptozotocin (STZ) (3 mg/kg) was used for induction of SAD in mice. Antia was injected intraperitoneally (i.p.) in 3 doses (25, 50, and 100 mg/kg/day) for 21 days. Neurobehavioral tests were conducted within 24 h after the last day of injection. Afterwards, mice were sacrificed and their hippocampi were rapidly excised, weighed, and homogenized to be used for measuring biochemical parameters. Results. Treatment with Antia significantly improved mice performance in the Morris water maze. In addition, biochemical analysis showed that Antia exerted a protective effect for several compounds, including GSH, MDA, NF-κB, IL-6, TNF-α, and amyloid β. Further studies with western blot showed the protective effect of Antia for the JAK2/STAT3 pathway. Conclusions. Antia exerts a significant protection against cognitive dysfunction induced by ICV-STZ injection. This effect is achieved through targeting of the amyloidogenic, inflammatory, and oxidative stress pathways. The JAK2/STAT3 pathway plays a protective role for neuroinflammatory and neurodegenerative diseases such as SAD.

scholarly journals Plasma contact factors as novel biomarkers for diagnosing Alzheimer’s disease

2021 ◽  
Vol 9 (1) ◽  
Author(s):  
Jung Eun Park ◽  
Do Sung Lim ◽  
Yeong Hee Cho ◽  
Kyu Yeong Choi ◽  
Jang Jae Lee ◽  
...  
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Early Stage ◽  
Clinical Stage ◽  
Area Under The Curve ◽  
Contact System ◽  
Plasma Diagnostic ◽  
Vascular Abnormalities ◽  
Prodromal Ad ◽  
Novel Biomarkers

Abstract Background Alzheimer’s disease (AD) is the most common cause of dementia and most of AD patients suffer from vascular abnormalities and neuroinflammation. There is an urgent need to develop novel blood biomarkers capable of diagnosing Alzheimer’s disease (AD) at very early stage. This study was performed to find out new accurate plasma diagnostic biomarkers for AD by investigating a direct relationship between plasma contact system and AD. Methods A total 101 of human CSF and plasma samples from normal and AD patients were analyzed. The contact factor activities in plasma were measured with the corresponding specific peptide substrates. Results The activities of contact factors (FXIIa, FXIa, plasma kallikrein) and FXa clearly increased and statistically correlated as AD progresses. We present here, for the first time, the FXIIa cut-off scores to as: > 26.3 U/ml for prodromal AD [area under the curve (AUC) = 0.783, p < 0.001] and > 27.2 U/ml for AD dementia (AUC = 0.906, p < 0.001). We also describe the cut-off scores from the ratios of CSF Aβ1–42 versus the contact factors. Of these, the representative ratio cut-off scores of Aβ1–42/FXIIa were to be: < 33.8 for prodromal AD (AUC = 0.965, p < 0.001) and < 27.44 for AD dementia (AUC = 1.0, p < 0.001). Conclusion The activation of plasma contact system is closely associated with clinical stage of AD, and FXIIa activity as well as the cut-off scores of CSF Aβ1–42/FXIIa can be used as novel accurate diagnostic AD biomarkers.

scholarly journals The Role of Salivary Biomarkers in the Early Diagnosis of Alzheimer’s Disease and Parkinson’s Disease

Diagnostics ◽  
2021 ◽  
Vol 11 (2) ◽  
pp. 371
Author(s):  
Patrycja Pawlik ◽  
Katarzyna Błochowiak
Keyword(s):  
Alzheimer’S Disease ◽  
Parkinson’S Disease ◽  
Alzheimer's Disease ◽  
Parkinson's Disease ◽  
Early Diagnosis ◽  
Neurodegenerative Diseases ◽  
Diagnostic Tool ◽  
Clinical Symptoms ◽  
Early Screening ◽  
Salivary Biomarkers

Many neurodegenerative diseases present with progressive neuronal degeneration, which can lead to cognitive and motor impairment. Early screening and diagnosis of neurodegenerative diseases such as Alzheimer’s disease (AD) and Parkinson’s disease (PD) are necessary to begin treatment before the onset of clinical symptoms and slow down the progression of the disease. Biomarkers have shown great potential as a diagnostic tool in the early diagnosis of many diseases, including AD and PD. However, screening for these biomarkers usually includes invasive, complex and expensive methods such as cerebrospinal fluid (CSF) sampling through a lumbar puncture. Researchers are continuously seeking to find a simpler and more reliable diagnostic tool that would be less invasive than CSF sampling. Saliva has been studied as a potential biological fluid that could be used in the diagnosis and early screening of neurodegenerative diseases. This review aims to provide an insight into the current literature concerning salivary biomarkers used in the diagnosis of AD and PD. The most commonly studied salivary biomarkers in AD are β-amyloid1-42/1-40 and TAU protein, as well as α-synuclein and protein deglycase (DJ-1) in PD. Studies continue to be conducted on this subject and researchers are attempting to find correlations between specific biomarkers and early clinical symptoms, which could be key in creating new treatments for patients before the onset of symptoms.

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