Heterogeneity of Cerebrospinal Fluid Biomarkers Profiles in Individuals with Distinct Levels of Cognitive Decline: A Cross-Sectional Study

2021 ◽  
pp. 1-14
Author(s):  
Marcos Vasconcelos Pais ◽  
Júlia Cunha Loureiro ◽  
Vagner Santigado do Vale ◽  
Marcia Radanovic ◽  
Leda Leme Talib ◽  
...  
Keyword(s):  
Cerebrospinal Fluid ◽  
Clinical Sample ◽  
Amyloid Β ◽  
Cross Sectional Study ◽  
Csf Biomarkers ◽  
Cross Sectional ◽  
Cerebrospinal Fluid Biomarkers ◽  
N Classification ◽  
T Tau ◽  
Phosphorylated Tau Protein

Background: Decreased cerebrospinal fluid (CSF) concentrations of the amyloid-β (Aβ), along with increased total (T-tau) and phosphorylated tau protein (P-tau), are widely accepted as core biomarkers of Alzheimer’s disease (AD) pathology. Nonetheless, there are a few remaining caveats that still preclude the full incorporation of AD biomarkers into clinical practice. Objective: To determine the frequency of clinical-biological mismatches in a clinical sample of older adults with varying degrees of cognitive impairment. Methods: 204 participants were enrolled for a cross-sectional assessment and allocated into diagnostic groups: probable AD (n = 60, 29.4%); MCI (n = 84, 41.2%); or normal cognition (NC, n = 60, 29.4%). CSF concentrations of Aβ 42, T-tau, and 181Thr-P-tau were determined, and Aβ 42/P-tau ratio below 9.53 was used as a proxy of AD pathology. The AT(N) classification was further used as a framework to ascertain the biological evidence of AD. Results: The majority (73.7%) of patients in the AD group had the Aβ 42/P-tau ratio below the cut-off score for AD, as opposed to a smaller proportion in the MCI (42.9%) and NC (23.3%) groups. In the latter, 21 subjects (35%) were classified as A+, 28 (46.7%) as T+, and 23 (38.3%) as N + . In the AD group, 66.7%of the cases were classified as A+, 78.3%as T+, and 80%as N+. Conclusion: Analysis of CSF biomarkers was able to discriminate between AD, MCI, and NC. However, clinical-biological mismatches were observed in a non-negligible proportion of cases.

scholarly journals A Comparison Between Tau and Amyloid-β Cerebrospinal Fluid Biomarkers in Chronic Traumatic Encephalopathy and Alzheimer Disease

2021 ◽  
Author(s):  
Katherine W. Turk ◽  
Alexandra Geada ◽  
Victor E. Alvarez ◽  
Weiming Xia ◽  
Jonathan D. Cherry ◽  
...  
Keyword(s):  
Cerebrospinal Fluid ◽  
Chronic Traumatic Encephalopathy ◽  
Amyloid Β ◽  
Cross Sectional Study ◽  
Meso Scale Discovery ◽  
Cross Sectional ◽  
Boston University ◽  
Cerebrospinal Fluid Biomarkers ◽  
Heart Study ◽  
T Tau

Abstract Background Cerebrospinal fluid (CSF) tau and beta-amyloid levels in chronic traumatic encephalopathy (CTE), a disease which can be clinically indistinguishable from Alzheimer’s disease (AD), are largely unknown. We examined postmortem CSF analytes among participants with autopsy confirmed CTE and AD. Methods In this cross-sectional study 192 participants from the Boston University AD Research Center, VA-BU-CLF Center, and Framingham Heart Study (FHS) had post-mortem CSF collected at autopsy. Participants were divided into pathological groups based on AD and CTE criteria, with 61 CTE participants (18 low, 43 high stage), 79 AD participants (23 low, 56 intermediate to high), 11 participants with CTE combined with AD, and 41 participants lacking both CTE and AD neuropathology. The Meso Scale Discovery immunoassay system was utilized to measure amyloid-beta (Aβ1 − 40, Aβ1 − 42), total tau (t-tau), and phosphorylated tau (p-tau181 and p-tau231). CSF analytes were then compared across the six pathological groups: no CTE/no AD, Low CTE, Low AD, High CTE, Intermediate/High AD, and AD + CTE. Results The low CTE group had higher levels of p-tau231 compared no CTE/no AD (p < 0.001), and compared to the low AD group (p = 0.002). The low CTE group had lower levels of Aβ1−42 compared to no CTE/no AD (p = 0.009). The high CTE group had higher levels of p-tau231 compared to intermediate/high AD (p < 0.001). Conclusions Importantly, p-tau231 and Aβ1−42 were predictors of diagnosis of CTE vs. no CTE/no AD and CTE vs. AD. Increased CSF p-tau231 is a promising potentially sensitive biomarker of CTE, and CSF Aβ1−42 needs further investigation in CTE.

scholarly journals Cerebrospinal fluid profiles with increasing number of cerebral microbleeds in a continuum of cognitive impairment

2015 ◽  
Vol 36 (3) ◽  
pp. 621-628 ◽  
Author(s):  
Sara Shams ◽  
Tobias Granberg ◽  
Juha Martola ◽  
Xiaozhen Li ◽  
Mana Shams ◽  
...  
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Cerebrospinal Fluid ◽  
Cognitive Impairment ◽  
Serum Albumin ◽  
Amyloid Β ◽  
Cerebral Microbleeds ◽  
Csf Biomarkers ◽  
Barrier Dysfunction ◽  
T Tau

Cerebral microbleeds (CMBs) are hypothesised to have an important yet unknown role in the dementia disease pathology. In this study we analysed increasing number of CMBs and their independent associations with routine cerebrospinal fluid (CSF) biomarkers in a continuum of cognitive impairment. A total of 1039 patients undergoing dementia investigation were analysed and underwent lumbar puncture, and an MRI scan. CSF samples were analysed for amyloid β (Aβ) 42, total tau (T-tau), tau phosphorylated at threonine 18 (P-tau) and CSF/serum albumin ratios. Increasing number of CMBs were independently associated with low Aβ42 levels, in the whole cohort, Alzheimer’s disease and mild cognitive impairment ( p < 0.05). CSF/serum albumin ratios were high with multiple CMBs ( p < 0.001), reflecting accompanying blood–brain barrier dysfunction. T-tau and P-tau levels were lower in Alzheimer’s patients with multiple CMBs when compared to zero CMBs, but did not change in the rest of the cohort. White matter hyperintensities were associated with low Aβ42 in the whole cohort and Alzheimer’s disease ( p < 0.05). Aβ42 is the routine CSF-biomarker mainly associated with CMBs in cognitive impairment, and there is an accumulative effect with increasing number of CMBs.

scholarly journals Cerebrospinal Fluid Biomarkers for Dementia with Lewy Bodies

2010 ◽  
Vol 2010 ◽  
pp. 1-17 ◽  
Author(s):  
Elizabeta B. Mukaetova-Ladinska ◽  
Rachael Monteith ◽  
Elaine K. Perry
Keyword(s):  
Cerebrospinal Fluid ◽  
Dementia With Lewy Bodies ◽  
Lewy Bodies ◽  
Low Frequency ◽  
Csf Biomarkers ◽  
Term Care ◽  
Clinical Criteria ◽  
Cerebrospinal Fluid Biomarkers ◽  
The Uk ◽  
T Tau

More than 750,000 of the UK population suffer from some form of cognitive impairment and dementia. Of these, 5–20% will have Dementia with Lewy Bodies (DLB). Clinico-pathological studies have shown that it is the low frequency of DLB clinical core features that makes the DLB diagnosis hardly recognisable during life, and easily misdiagnosed for other forms of dementia. This has an impact on the treatment and long-term care of the affected subjects. Having a biochemical test, based on quantification of a specific DLB biomarker within Cerebrospinal Fluid (CSF) could be an effective diagnostic method to improve the differential diagnosis. Although some of the investigated DLB CSF biomarkers are well within the clinical criteria for sensitivity and specificity (90%), they all seem to be confounded by the contradictory data for each of the major groups of biomarkers (-synuclein, tau and amyloid proteins). However, a combination of CSF measures appear to emerge, that may well be able to differentiate DLB from other dementias: -synuclein reduction in early DLB, a correlation between CSF -synuclein and A42 measures (characteristic for DLB only), and t-tau and p-tau181 profile (differentiating AD from DLB).

scholarly journals Role of cerebrospinal fluid biomarkers to predict conversion to dementia in patients with mild cognitive impairment: a clinical cohort study

2015 ◽  
Vol 53 (3) ◽  
Author(s):  
Manuela Tondelli ◽  
Roberta Bedin ◽  
Annalisa Chiari ◽  
Maria Angela Molinari ◽  
Guendalina Bonifacio ◽  
...  
Keyword(s):  
Cerebrospinal Fluid ◽  
Csf Biomarkers ◽  
Neuropsychological Evaluation ◽  
Neurological Assessment ◽  
Blood Tests ◽  
Clinical Cohort ◽  
Cerebrospinal Fluid Biomarkers ◽  
Csf Levels ◽  
T Tau

AbstractCerebrospinal fluid (CSF) levels assessment of AβA group of 71 MCI patients underwent neurological assessment, extended neuropsychological evaluation, routine blood tests, ApoE determination, and lumbar puncture to dose t-tau, p-tauBaseline AβOur results confirm the key role of CSF biomarkers in predicting patient conversion from MCI to dementia. The study suggests that CSF biomarkers may also be reliable in a real world clinical setting.

Relationship Between General Cognition, Visual Assessed Cortical Atrophy, and Cerebrospinal Fluid Biomarkers in Alzheimer’s Disease: A Cross-Sectional Study from a Chinese PUMCH Cohort

2021 ◽  
pp. 1-10
Author(s):  
Chenhui Mao ◽  
Longze Sha ◽  
Jie Li ◽  
Xinying Huang ◽  
Shanshan Chu ◽  
...  
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Cerebrospinal Fluid ◽  
Rating Scales ◽  
Mmse Score ◽  
Cortical Atrophy ◽  
Csf Biomarkers ◽  
Cortical Region ◽  
Cross Sectional ◽  
T Tau

Background: Cerebrospinal fluid (CSF) biomarkers are widely accepted as manifestations of Alzheimer’s disease (AD) pathogenesis and incorporated into biological definition of AD. However, the correlations between CSF and other biomarkers such as neuroimaging and neuropsychiatric evaluation are complicated and inconsistent. Objective: We aimed to better interpreting CSF biomarkers results accompanying with other indexes in improving accurate diagnosis of AD. Methods: 112 AD patients and 30 cognitive normal controls were selected. Commercial accessible ELISA kits were introduced for measurement of CSF t-tau, p-tau181, Aβ 1–42, and NfL based on standard protocol. MRI examinations were performed using a 3-T MRI scanner and visual rating scales including medial temporal atrophy score and Koedam’s scale were used to evaluate medial temporal atrophy and posterior region atrophy. Results: CSF biomarkers’ profile including decreased concentration of Aβ 1–42, increased concentration of t-tau, p-tau181, t-tau/Aβ 1–42, and NfL were diagnostic between AD and control. CSF biomarkers profile was not influenced by the APOE genotype. Increased concentration of t-tau and NfL, as well as ratio of t-tau/Aβ 1–42 were related to decrease of Mini-Mental State Examination (MMSE) score while concentration of Aβ 1–42 not. Visual assessed cortical atrophy was related to MMSE score, but most of the CSF biomarkers were not related to atrophy, except that increased concentration of p-tau181 was significantly associated with atrophy of posterior cortical region. Conclusion: Our results supported CSF biomarkers were helpful in diagnosis of AD. However, CSF biomarkers were cross-sectional reflection of pathogenesis, which did not correlate well with clinical progression. CSF biomarkers should be interpreted in combination with MRI and cognitive evaluation in clinical use.

scholarly journals Cognitively unimpaired individuals with a low burden of Aβ pathology have a distinct CSF biomarker profile

2021 ◽  
Vol 13 (1) ◽  
Author(s):  
Marta Milà-Alomà ◽  
Mahnaz Shekari ◽  
Gemma Salvadó ◽  
Juan Domingo Gispert ◽  
Eider M. Arenaza-Urquijo ◽  
...  
Keyword(s):  
Functional Neuroimaging ◽  
Amyloid Β ◽  
Structural Mri ◽  
Cross Sectional Study ◽  
Cognitive Assessments ◽  
Cross Sectional ◽  
Neurofilament Light ◽  
Functional Changes ◽  
Downstream Effects ◽  
T Tau

Abstract Background Understanding the changes that occur in the transitional stage between absent and overt amyloid-β (Aβ) pathology within the Alzheimer’s continuum is crucial to develop therapeutic and preventive strategies. The objective of this study is to test whether cognitively unimpaired individuals with a low burden of Aβ pathology have a distinct CSF, structural, and functional neuroimaging biomarker profile. Methods Cross-sectional study of 318 middle-aged, cognitively unimpaired individuals from the ALFA+ cohort. We measured CSF Aβ42/40, phosphorylated tau (p-tau), total tau (t-tau), neurofilament light (NfL), neurogranin, sTREM2, YKL40, GFAP, IL6, S100B, and α-synuclein. Participants also underwent cognitive assessments, APOE genotyping, structural MRI, [18F]-FDG, and [18F]-flutemetamol PET. To ensure the robustness of our results, we used three definitions of low burden of Aβ pathology: (1) positive CSF Aβ42/40 and < 30 Centiloids in Aβ PET, (2) positive CSF Aβ42/40 and negative Aβ PET visual read, and (3) 20–40 Centiloid range in Aβ PET. We tested CSF and neuroimaging biomarker differences between the low burden group and the corresponding Aβ-negative group, adjusted by age and sex. Results The prevalence and demographic characteristics of the low burden group differed between the three definitions. CSF p-tau and t-tau were increased in the low burden group compared to the Aβ-negative in all definitions. CSF neurogranin was increased in the low burden group definitions 1 and 3, while CSF NfL was only increased in the low burden group definition 1. None of the defined low burden groups showed signs of atrophy or glucose hypometabolism. Instead, we found slight increases in cortical thickness and metabolism in definition 2. Conclusions There are biologically meaningful Aβ-downstream effects in individuals with a low burden of Aβ pathology, while structural and functional changes are still subtle or absent. These findings support considering individuals with a low burden of Aβ pathology for clinical trials. Trial registration NCT02485730

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.

scholarly journals Cerebrospinal Fluid Tau and Amyloid β Proteins Do Not Correlate With Cognitive Functioning in Cognitively Impaired Memory Clinic Patients

CNS Spectrums ◽  
2010 ◽  
Vol 15 (9) ◽  
pp. 588-593 ◽  
Author(s):  
Petra E. Spies ◽  
Jurgen A.H.R. Claassen ◽  
Diane Slats ◽  
Marcel G.M. Olde Rikkert ◽  
Marcel M. Verbeek ◽  
...  
Keyword(s):  
Cerebrospinal Fluid ◽  
Cognitive Impairment ◽  
Cognitive Functioning ◽  
Neuronal Damage ◽  
Amyloid Β ◽  
Absolute Amount ◽  
Csf Biomarkers ◽  
Memory Clinic ◽  
Compensatory Mechanisms ◽  
T Tau

ABSTRACTObjective: The aim of this study was to investigate the influence of cerebrospinal fluid (CSF), amyloid β42(Aβ42), phosphorylated tau181 (p-tau), and total tau (t-tau) on cognitive functioning.Methods: We analyzed the ability of the CSF biomarkers Aβ42, p-tau, and t-tau to predict the results on the Cambridge Cognitive Examination–Revised (CAMCOG-R), a cognitive screening test that assesses multiple cognitive domains, in 65 memory clinic patients (73.1±8.2 years) (n=30 probable Alzheimer's disease [AD], n=7 possible AD, n=12 non-AD dementia, n=16 mild cognitive impairment).Results: We found no correlations between CSF biomarkers and CAMCOG-R performance in the whole group, nor in subgroups based on aberrant biomarker concentrations.Discussion: Changed concentrations of CSF amyloid β42, p-tau, and t-tau cannot be directly linked to cognitive function in our sample of patients with cognitive impairment. Possibly, compensatory mechanisms such as cognitive reserve determine cognitive performance, rather than the absolute amount of damage caused by Aβ deposition and tangle formation. In addition, abnormal CSF biomarker concentrations may not be a direct reflection of the amount of neuronal damage, but merely serve as an indicator of AD pathology.Conclusion: While CSF biomarkers are valuable in establishing AD pathology, they cannot be used to predict severity of cognitive impairment.

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

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