scholarly journals Association of lysophosphatidic acids with cerebrospinal fluid biomarkers and progression to Alzheimer’s disease

2020 ◽  
Vol 12 (1) ◽  
Author(s):  
Shahzad Ahmad ◽  
Adelina Orellana ◽  
Isabelle Kohler ◽  
Lutz Frölich ◽  
Itziar de Rojas ◽  
...  
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Cerebrospinal Fluid ◽  
Positive Association ◽  
Csf Biomarkers ◽  
Liquid Chromatography Mass Spectrometry ◽  
Significant Positive Association ◽  
Total Tau ◽  
Cerebrospinal Fluid Biomarkers ◽  
Independent Cohort

Abstract Background Lysophosphatidic acids (LPAs) are bioactive signaling phospholipids that have been implicated in Alzheimer’s disease (AD). It is largely unknown whether LPAs are associated with AD pathology and progression from mild cognitive impairment (MCI) to AD. Methods The current study was performed on cerebrospinal fluid (CSF) and plasma samples of 182 MCI patients from two independent cohorts. We profiled LPA-derived metabolites using liquid chromatography-mass spectrometry. We evaluated the association of LPAs with CSF biomarkers of AD, Aβ-42, p-tau, and total tau levels overall and stratified by APOE genotype and with MCI to AD progression. Results Five LPAs (C16:0, C16:1, C22:4, C22:6, and isomer-LPA C22:5) showed significant positive association with CSF biomarkers of AD, Aβ-42, p-tau, and total tau, while LPA C14:0 and C20:1 associated only with Aβ-42 and alkyl-LPA C18:1, and LPA C20:1 associated with tau pathology biomarkers. Association of cyclic-LPA C16:0 and two LPAs (C20:4, C22:4) with Aβ-42 levels was found only in APOE ε4 carriers. Furthermore, LPA C16:0 and C16:1 also showed association with MCI to AD dementia progression, but results did not replicate in an independent cohort. Conclusions Our findings provide evidence that LPAs may contribute to early AD pathogenesis. Future studies are needed to determine whether LPAs play a role in upstream of AD pathology or are downstream markers of neurodegeneration.

scholarly journals Integrated proteomics reveals brain-based cerebrospinal fluid biomarkers in asymptomatic and symptomatic Alzheimer’s disease

2020 ◽  
Vol 6 (43) ◽  
pp. eaaz9360 ◽  
Author(s):  
Lenora Higginbotham ◽  
Lingyan Ping ◽  
Eric B. Dammer ◽  
Duc M. Duong ◽  
Maotian Zhou ◽  
...  
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Cerebrospinal Fluid ◽  
Wide Spectrum ◽  
Csf Biomarkers ◽  
Protein Biomarkers ◽  
Cerebrospinal Fluid Biomarkers ◽  
Brain Proteome ◽  
The Brain ◽  
Underlying Pathophysiology

Alzheimer’s disease (AD) lacks protein biomarkers reflective of its diverse underlying pathophysiology, hindering diagnostic and therapeutic advancements. Here, we used integrative proteomics to identify cerebrospinal fluid (CSF) biomarkers representing a wide spectrum of AD pathophysiology. Multiplex mass spectrometry identified ~3500 and ~12,000 proteins in AD CSF and brain, respectively. Network analysis of the brain proteome resolved 44 biologically diverse modules, 15 of which overlapped with the CSF proteome. CSF AD markers in these overlapping modules were collapsed into five protein panels representing distinct pathophysiological processes. Synaptic and metabolic panels were decreased in AD brain but increased in CSF, while glial-enriched myelination and immunity panels were increased in brain and CSF. The consistency and disease specificity of panel changes were confirmed in >500 additional CSF samples. These panels also identified biological subpopulations within asymptomatic AD. Overall, these results are a promising step toward a network-based biomarker tool for AD clinical applications.

scholarly journals Clinical and biological predictors of Alzheimer's disease in patients with amnestic mild cognitive impairment

2010 ◽  
Vol 32 (3) ◽  
pp. 216-222 ◽  
Author(s):  
Orestes V. Forlenza ◽  
Breno S. Diniz ◽  
Leda L. Talib ◽  
Marcia Radanovic ◽  
Monica S. Yassuda ◽  
...  
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Cerebrospinal Fluid ◽  
Cognitive Impairment ◽  
Mild Cognitive Impairment ◽  
Amnestic Mild Cognitive Impairment ◽  
Total Tau ◽  
Cerebrospinal Fluid Biomarkers ◽  
Antidementia Drugs ◽  
Beta Peptide

OBJECTIVE: To identify predictors of the progression from pre-dementia stages of cognitive impairment in Alzheimer's disease is relevant to clinical management and to substantiate the decision of prescribing antidementia drugs. METHOD: Longitudinal study of a cohort of elderly adults with amnestic mild cognitive impairment and healthy controls, carried out to estimate the risk and characterize predictors of the progression to Alzheimer's disease. RESULTS: Patients with amnestic mild cognitive impairment had a higher risk to develop Alzheimer's disease during follow-up (odds ratio = 4.5, CI95% [1.3-13.6], p = 0.010). At baseline, older age, lower scores on memory tests and presence of the APOE*4 allele predicted the progression from amnestic mild cognitive impairment to Alzheimer's disease. In a sub sample of amnestic mild cognitive impairment patients, those who progressed to Alzheimer's disease had lower cerebrospinal fluid concentrations of amyloid-beta peptide (Aβ42, p = 0.020) and higher concentrations of total TAU (p = 0.030) and phosphorylated TAU (p = 0.010), as compared to non-converters. DISCUSSION: This is the first Brazilian study to report cerebrospinal fluid biomarkers in the prediction of the conversion from MCI to Alzheimer's disease. Our data are in accordance with those reported in other settings. The measurement of cerebrospinal fluid total-TAU, phospho-TAU and Aβ42 may help identify patients with mild cognitive impairment at higher risk for developing Alzheimer's disease.

scholarly journals Quantitative Appraisal of Ventricular Cerebrospinal Fluid Biomarkers in Neuropathologically Diagnosed Parkinson's Disease Cases Lacking Alzheimer's Disease Pathology

2013 ◽  
Vol 8 ◽  
pp. BMI.S11422 ◽  
Author(s):  
Chera L. Maarouf ◽  
Thomas G. Beach ◽  
Charles H. Adler ◽  
Michael Malek-Ahmadi ◽  
Tyler A. Kokjohn ◽  
...  
Keyword(s):  
Alzheimer’S Disease ◽  
Parkinson’S Disease ◽  
Alzheimer's Disease ◽  
Parkinson's Disease ◽  
Cerebrospinal Fluid ◽  
Early Stage ◽  
Csf Biomarkers ◽  
Cerebrospinal Fluid Biomarkers ◽  
Proteomic Study ◽  
Quantitative Appraisal

Identifying biomarkers that distinguish Parkinson's disease (PD) from normal control (NC) individuals has the potential to increase diagnostic sensitivity for the detection of early-stage PD. A previous proteomic study identified potential biomarkers in postmortem ventricular cerebrospinal fluid (V-CSF) from neuropathologically diagnosed PD subjects lacking Alzheimer's disease (AD) neuropathology. In the present study, we assessed these biomarkers as well as p-tau181, Aβ42, and S100B by ELISA in PD (n = 43) and NC (n = 49) cases. The p-tau181/Aβ42 ratio and ApoA-1 showed statistically significant differences between groups. Multiple regression analysis demonstrated that p-tau181/Aβ42 had a significant odds ratio: OR = 1.42 (95% confidence interval [CI], 1.12–1.84), P = 0.006. Among the molecules investigated, intriguing correlations were observed that require further investigation. Our results suggest coexistent AD CSF biomarkers within the PD group notwithstanding that it was selected to minimize AD neuropathological lesions.

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.

scholarly journals Midlife Stress in Relation to Late-Life Cerebrospinal Fluid Biomarkers of Alzheimer’s Disease: A 25-Year Follow-Up Study

2018 ◽  
Vol 46 (1-2) ◽  
pp. 90-99 ◽  
Author(s):  
Lena Johansson ◽  
Silke Kern ◽  
Henrik Zetterberg ◽  
Kaj Blennow ◽  
Anne Börjesson-Hansson ◽  
...  
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Cerebrospinal Fluid ◽  
Psychological Stress ◽  
Late Life ◽  
Csf Biomarkers ◽  
Linear Regression Models ◽  
Cerebrospinal Fluid Biomarkers ◽  
T Tau

Background/Aims: Psychological stress has previously been associated with higher risk of developing late-life dementia, especially Alzheimer’s disease (AD). This study tested whether longstanding midlife stress is related to cerebrospinal fluid (CSF) biomarkers of late-life AD, such as tau protein and amyloid beta (Aβ). Methods: The study included 79 nondemented females from the Prospective Population Study of Women in Gothenburg, Sweden, who responded to a standardized stress question at baseline (mean age 49 years) and underwent a lumbar puncture at follow-up 25 years later. Multiple linear regression models analyzed the relationships between midlife psychological stress and late-life CSF measures of total tau (t-tau), phosphorylated tau (p-tau), Aβ40, and Aβ42. Results: Longstanding stress in midlife was associated with higher levels of CSF t-tau (β = 0.64, p = 0.01) and Aβ40 (β = 0.60, p = 0.02) in late life. No associations were found between midlife stress and levels of p-tau or Aβ42. Conclusion: The findings suggest that longstanding stress stimulates unspecific neurodegenerative processes, but not the core processes of AD, at least not in the early phase of the disease. The association with higher concentration of CSF t-tau may reflect neural degeneration and the association with higher Aβ40 may be an early sign of Aβ overproduction or cerebrovascular processes in the brain.

A worldwide multicentre comparison of assays for cerebrospinal fluid biomarkers in Alzheimer's disease

2009 ◽  
Vol 46 (3) ◽  
pp. 235-240 ◽  
Author(s):  
N A Verwey ◽  
W M van der Flier ◽  
K Blennow ◽  
C Clark ◽  
S Sokolow ◽  
...  
Keyword(s):  
Alzheimer’S Disease ◽  
Quality Control ◽  
Cerebrospinal Fluid ◽  
Amyloid Beta ◽  
Csf Biomarkers ◽  
Total Tau ◽  
Cerebrospinal Fluid Biomarkers ◽  
Control Programmes ◽  
Analytical Procedures ◽  
Immunosorbent Assays

Background Different cerebrospinal fluid (CSF) amyloid-beta 1–42 (A β1–42), total Tau (Tau) and Tau phosphorylated at threonine 181 (P-Tau) levels are reported, but currently there is a lack of quality control programmes. The aim of this study was to compare the measurements of these CSF biomarkers, between and within centres. Methods Three CSF-pool samples were distributed to 13 laboratories in 2004 and the same samples were again distributed to 18 laboratories in 2008. In 2004 six laboratories measured A β1–42, Tau and P-Tau and seven laboratories measured one or two of these marker(s) by enzyme-linked immunosorbent assays (ELISAs). In 2008, 12 laboratories measured all three markers, three laboratories measured one or two marker(s) by ELISAs and three laboratories measured the markers by Luminex. Results In 2004, the ELISA intercentre coefficients of variance (interCV) were 31%, 21% and 13% for A β1–42, Tau and P-Tau, respectively. These were 37%, 16% and 15%, respectively, in 2008. When we restricted the analysis to the Innotest® ( N = 13) for A β1–42, lower interCV were calculated (22%). The centres that participated in both years ( N = 9) showed interCVs of 21%, 15% and 9% and intra-centre coefficients (intraCV) of variance of 25%,18% and 7% in 2008. Conclusions The highest variability was found for A β1–42. The variabilities for Tau and P-Tau were lower in both years. The centres that participated in both years showed a high intraCV comparable to their interCV, indicating that there is not only a high variation between but also within centres. Besides a uniform standardization of (pre)analytical procedures, the same assay should be used to decrease the inter/intracentre variation.

Cerebrospinal Fluid Biomarkers of Alzheimer’s Disease Correlate With Electroencephalography Parameters Assessed by Exact Low-Resolution Electromagnetic Tomography (eLORETA)

2016 ◽  
Vol 48 (5) ◽  
pp. 338-347 ◽  
Author(s):  
Masahiro Hata ◽  
Toshihisa Tanaka ◽  
Hiroaki Kazui ◽  
Ryouhei Ishii ◽  
Leonides Canuet ◽  
...  
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Cerebrospinal Fluid ◽  
Csf Biomarkers ◽  
Low Resolution ◽  
Temporal Area ◽  
Electromagnetic Tomography ◽  
Total Tau ◽  
Study Results ◽  
The Right

Recently, cerebrospinal fluid (CSF) biomarkers related to Alzheimer’s disease (AD) have garnered a lot of clinical attention. To explore neurophysiological traits of AD and parameters for its clinical diagnosis, we examined the association between CSF biomarkers and electroencephalography (EEG) parameters in 14 probable AD patients. Using exact low-resolution electromagnetic tomography (eLORETA), artifact-free 40-sesond EEG data were estimated with current source density (CSD) and lagged phase synchronization (LPS) as the EEG parameters. Correlations between CSF biomarkers and the EEG parameters were assessed. Patients with AD showed significant negative correlation between CSF beta-amyloid (Aβ)-42 concentration and the logarithms of CSD over the right temporal area in the theta band. Total tau concentration was negatively correlated with the LPS between the left frontal eye field and the right auditory area in the alpha-2 band in patients with AD. Our study results suggest that AD biomarkers, in particular CSF Aβ42 and total tau concentrations are associated with the EEG parameters CSD and LPS, respectively. Our results could yield more insights into the complicated pathology of AD.

scholarly journals Cerebrospinal Fluid Biomarkers for Diagnosis of Alzheimer’s Disease

2015 ◽  
Vol 31 (1) ◽  
pp. 34-41
Author(s):  
Imran Sarker ◽  
Md Rezaul Karim Khan ◽  
Anisul Haque ◽  
Md Rafiqul Islam
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Cerebrospinal Fluid ◽  
Senile Plaques ◽  
Disease Diagnosis ◽  
Diagnostic Tools ◽  
Csf Biomarkers ◽  
Diagnostic Potential ◽  
Cerebrospinal Fluid Biomarkers ◽  
T Tau

Alzheimer’s disease is the most common cause of dementia among elderly people. The major pathological hallmarks of AD are the loss of neurons, occurrence of extracellular senile plaques as well as intracellular neurofibrillary tangles (NFT). Biochemical changes in the brain are reflected in the cerebrospinal fluid (CSF), and intense research efforts have been made to develop biomarkers for the central pathogenic processes in AD that can be used as diagnostic tools. Biomarkers are essential part of disease management as they are essential for diagnosis, monitoring the disease progression, detecting early onset of the disease, monitoring the effect of therapeutic intervention, and also avoiding false diagnosis of the disease. Unfortunately, none of the biomarkers presently available are able to accomplish the disease diagnosis single-handedly. Three CSF biomarkers, Aâ42, Total-tau (t-tau), and phosphorylated-tau (p-tau), have been found to have the highest diagnostic potential. Bangladesh Journal of Neuroscience 2015; Vol. 31 (1): 34-41

scholarly journals From Cerebrospinal Fluid Neurochemistry to Clinical Diagnosis of Alzheimer’s Disease in the Era of Anti-Amyloid Treatments. Report of Four Patients

Biomedicines ◽  
2021 ◽  
Vol 9 (10) ◽  
pp. 1376
Author(s):  
Ioanna Tsantzali ◽  
Fotini Boufidou ◽  
Eleni Sideri ◽  
Antonis Mavromatos ◽  
Myrto G. Papaioannou ◽  
...  
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Cerebrospinal Fluid ◽  
Clinical Presentation ◽  
Diagnostic System ◽  
Amyloid Peptide ◽  
Correct Identification ◽  
Total Tau ◽  
Cerebrospinal Fluid Biomarkers ◽  
Disease Modifying Treatment

Analysis of classical cerebrospinal fluid biomarkers, especially when incorporated in a classification/diagnostic system such as the AT(N), may offer a significant diagnostic tool allowing correct identification of Alzheimer’s disease during life. We describe four patients with more or less atypical or mixed clinical presentation, in which the classical cerebrospinal fluid biomarkers amyloid peptide with 42 and 40 amino acids (Aβ42 and Aβ40, respectively), phospho-tau (τP-181) and total tau (τΤ) were measured. Despite the unusual clinical presentation, the biomarker profile was compatible with Alzheimer’s disease in all four patients. The measurement of classical biomarkers in the cerebrospinal fluid may be a useful tool in identifying the biochemical fingerprints of Alzheimer’s disease, especially currently, due to the recent approval of the first disease-modifying treatment, allowing not only typical but also atypical cases to be enrolled in trials of such treatments.

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