Cerebrospinal Fluid Amyloid-β Subtypes in Confirmed Frontotemporal Lobar Degeneration Cases: A Pilot Study

2019 ◽  
Vol 71 (1) ◽  
pp. 15-20
Author(s):  
Nicolaas A. Verwey ◽  
Charlotte E. Teunissen ◽  
Jeroen J.M. Hoozemans ◽  
Annemieke J.M. Rozemuller ◽  
Philip Scheltens ◽  
...  
Keyword(s):  
Cerebrospinal Fluid ◽  
Pilot Study ◽  
Frontotemporal Lobar Degeneration ◽  
Amyloid Β

Tau Rather than TDP-43 Proteins are Potential Cerebrospinal Fluid Biomarkers for Frontotemporal Lobar Degeneration Subtypes: A Pilot Study

2016 ◽  
Vol 55 (2) ◽  
pp. 585-595 ◽  
Author(s):  
H. Bea Kuiperij ◽  
Alexandra A.M. Versleijen ◽  
Marijke Beenes ◽  
Nicolaas A. Verwey ◽  
Luisa Benussi ◽  
...  
Keyword(s):  
Cerebrospinal Fluid ◽  
Pilot Study ◽  
Frontotemporal Lobar Degeneration ◽  
Cerebrospinal Fluid Biomarkers

scholarly journals ATN status in amnestic and non-amnestic Alzheimer’s disease and frontotemporal lobar degeneration

2019 ◽  
Author(s):  
Katheryn A.Q. Cousins ◽  
David J. Irwin ◽  
David A. Wolk ◽  
Edward B. Lee ◽  
Leslie M.J. Shaw ◽  
...  
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Cerebrospinal Fluid ◽  
Frontotemporal Lobar Degeneration ◽  
Operating Characteristic ◽  
Characteristic Curve ◽  
Amyloid Β ◽  
Phosphorylated Tau ◽  
Total Tau ◽  
Operating Characteristic Curve

AbstractUnder the ATN framework, cerebrospinal fluid analytes provide evidence of the presence or absence of Alzheimer’s disease pathological hallmarks: amyloid plaques (A), phosphorylated tau (T), and accompanying neurodegeneration (N). Still, differences in cerebrospinal fluid levels across amnestic and non-amnestic variants or due to co-occurring pathologies might lead to misdiagnoses. We assess the diagnostic accuracy of cerebrospinal fluid markers for amyloid, tau, and neurodegeneration in an autopsy cohort of 118 Alzheimer’s disease patients (98 amnestic; 20 non-amnestic) and 64 frontotemporal lobar degeneration patients (five amnestic; 59 non-amnestic). We calculated between-group differences in cerebrospinal fluid concentrations of amyloid-β1–42 peptide, tau protein phosphorylated at threonine 181, total tau, and the ratio of phosphorylated tau to amyloid-β1–42. Results show that non-amnestic Alzheimer’s disease patients were less likely to be correctly classified under the ATN framework using independent, published biomarker cutoffs for positivity. Amyloid-β1–42 did not differ between amnestic and non-amnestic Alzheimer’s disease, and receiver operating characteristic curve analyses indicated that amyloid-β1–42 was equally effective in discriminating both groups from frontotemporal lobar degeneration. However, cerebrospinal fluid concentrations of phosphorylated tau, total tau, and the ratio of phosphorylated tau to amyloid-β1–42 were significantly lower in non-amnestic compared to amnestic Alzheimer’s disease patients. Receiver operating characteristic curve analyses for these markers showed reduced area under the curve when discriminating non-amnestic Alzheimer’s disease from frontotemporal lobar degeneration, compared to discrimination of amnestic Alzheimer’s disease from frontotemporal lobar degeneration. In addition, the ATN framework was relatively insensitive to frontotemporal lobar degeneration, and these patients were likely to be classified as having normal biomarkers or biomarkers suggestive of primary Alzheimer’s disease pathology. We conclude that amyloid-β1–42 maintains high sensitivity to A status, although with lower specificity, and this single biomarker provides better sensitivity to non-amnestic Alzheimer’s disease than either the ATN framework or the phosphorylated-tau/amyloid-β1–42 ratio. In contrast, T and N status biomarkers differed between amnestic and non-amnestic Alzheimer’s disease; standard cutoffs for phosphorylated tau and total tau may thus result in misclassifications for non-amnestic Alzheimer’s patients. Consideration of clinical syndrome may help improve the accuracy of ATN designations for identifying true non-amnestic Alzheimer’s disease.Abbreviated SummaryCousins et al. assess the 2018 ATN framework and find that non-amnestic patients with Alzheimer’s disease (AD) have lower cerebrospinal fluid (CSF) phosphorylated tau and total tau than amnestic AD, while CSF amyloid-β accurately stratifies both non-amnestic and amnestic AD from frontotemporal lobar degeneration.

scholarly journals Prediction of P-tau/Aβ42 in the cerebrospinal fluid with blood microRNAs in Alzheimer’s disease

BMC Medicine ◽  
2021 ◽  
Vol 19 (1) ◽  
Author(s):  
Longfei Jia ◽  
Min Zhu ◽  
Jianwei Yang ◽  
Yana Pang ◽  
Qi Wang ◽  
...  
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Cerebrospinal Fluid ◽  
Pilot Study ◽  
Predictive Model ◽  
Amyloid Β ◽  
Positron Emission Tomography Imaging ◽  
Positron Emission ◽  
Diagnostic Capacity ◽  
Predicted Values

Abstract Background The most common biomarkers of Alzheimer’s disease (AD) are amyloid β (Aβ) and tau, detected in cerebrospinal fluid (CSF) or with positron emission tomography imaging. However, these procedures are invasive and expensive, which hamper their availability to the general population. Here, we report a panel of microRNAs (miRNAs) in serum that can predict P-tau/Aβ42 in CSF and readily differentiate AD from other dementias, including vascular dementia (VaD), Parkinson disease dementia (PDD), behavioral variant frontotemporal dementia (bvFTD), and dementia with Lewy body (DLB). Methods RNA samples were extracted from the participant’s blood. P-tau/Aβ42 of CSF was examined for diagnostic purposes. A pilot study (controls, 21; AD, 23), followed by second (controls, 216; AD, 190) and third groups (controls, 153; AD, 151), is used to establish and verify a predictive model of P-tau/Aβ42 in CSF. The test is then applied to a fourth group of patients with different dementias (controls, 139; AD,155; amnestic mild cognitive impairment [aMCI], 55; VaD, 51; PDD, 53; bvFTD, 53; DLB, 52) to assess its diagnostic capacity. Results In the pilot study, 29 upregulated and 31 downregulated miRNAs in the AD group were found. In Dataset 2, these miRNAs were then included as independent variables in the linear regression model. A seven-microRNA panel (miR-139-3p, miR-143-3p, miR-146a-5p, miR-485-5p, miR-10a-5P, miR-26b-5p, and miR-451a-5p) accurately predicted values of P-tau/Aβ42 of CSF. In Datasets 3 and 4, by applying the predicted P-tau/Aβ42, the predictive model successfully differentiates AD from controls and VaD, PDD, bvFTD, and DLB. Conclusions This study suggests that the panel of microRNAs is a promising substitute for traditional measurement of P-tau/Aβ42 in CSF as an effective biomarker of AD.

scholarly journals Effect of sleep on overnight cerebrospinal fluid amyloid β kinetics

2018 ◽  
Vol 83 (1) ◽  
pp. 197-204 ◽  
Author(s):  
Brendan P. Lucey ◽  
Terry J. Hicks ◽  
Jennifer S. McLeland ◽  
Cristina D. Toedebusch ◽  
Jill Boyd ◽  
...  
Keyword(s):  
Cerebrospinal Fluid ◽  
Amyloid Β

Age-Dependency of Total Tau in the Cerebrospinal Fluid Is Corrected by Amyloid-β 1–40: A Correlational Study in Healthy Adults

2021 ◽  
pp. 1-8
Author(s):  
Paul Theo Zebhauser ◽  
Achim Berthele ◽  
Marie-Sophie Franz ◽  
Oliver Goldhardt ◽  
Janine Diehl-Schmid ◽  
...  
Keyword(s):  
Cerebrospinal Fluid ◽  
Amyloid Β ◽  
Healthy Adults ◽  
Tau Proteins ◽  
Clinical Settings ◽  
Inclusion Criteria ◽  
Total Tau ◽  
Potential Marker ◽  
Wide Range ◽  
The Relationship

Background: Tau proteins are established biomarkers of neuroaxonal damage in a wide range of neurodegenerative conditions. Although measurement of total-Tau in the cerebrospinal fluid is widely used in research and clinical settings, the relationship between age and total-Tau in the cerebrospinal fluid is yet to be fully understood. While past studies reported a correlation between age and total-Tau in the cerebrospinal fluid of healthy adults, in clinical practice the same cut-off value is used independently of patient’s age. Objective: To further explore the relationship between age and total-Tau and to disentangle neurodegenerative from drainage-dependent effects. Methods: We analyzed cerebrospinal fluid samples of 76 carefully selected cognitively healthy adults and included amyloid-β 1–40 as a potential marker of drainage from the brain’s interstitial system. Results: We found a significant correlation of total-Tau and age, which was no longer present when correcting total-Tau for amyloid-β 1–40 concentrations. These findings were replicated under varied inclusion criteria. Conclusion: Results call into question the association of age and total-Tau in the cerebrospinal fluid. Furthermore, they suggest diagnostic utility of amyloid-β 1–40 as a possible proxy for drainage-mechanisms into the cerebrospinal fluid when interpreting biomarker concentrations for neurodegenerative diseases.

scholarly journals Shear-Induced Amyloid Aggregation in the Brain: V. Are Alzheimer’s and Other Amyloid Diseases Initiated in the Lower Brain and Brainstem by Cerebrospinal Fluid Flow Stresses?

2020 ◽  
pp. 1-24
Author(s):  
Conrad N. Trumbore
Keyword(s):  
Cerebrospinal Fluid ◽  
Conformational Changes ◽  
Extensional Flow ◽  
Amyloid Β ◽  
High Energy ◽  
Mechanical Agitation ◽  
Cerebrospinal Fluid Flow ◽  
Pulse Waves ◽  
Amyloid Diseases ◽  
The Brain

Amyloid-β (Aβ) and tau oligomers have been identified as neurotoxic agents responsible for causing Alzheimer’s disease (AD). Clinical trials using Aβ and tau as targets have failed, giving rise to calls for new research approaches to combat AD. This paper provides such an approach. Most basic AD research has involved quiescent Aβ and tau solutions. However, studies involving laminar and extensional flow of proteins have demonstrated that mechanical agitation of proteins induces or accelerates protein aggregation. Recent MRI brain studies have revealed high energy, chaotic motion of cerebrospinal fluid (CSF) in lower brain and brainstem regions. These and studies showing CSF flow within the brain have shown that there are two energetic hot spots. These are within the third and fourth brain ventricles and in the neighborhood of the circle of Willis blood vessel region. These two regions are also the same locations as those of the earliest Aβ and tau AD pathology. In this paper, it is proposed that cardiac systolic pulse waves that emanate from the major brain arteries in the lower brain and brainstem regions and whose pulse waves drive CSF flows within the brain are responsible for initiating AD and possibly other amyloid diseases. It is further proposed that the triggering of these diseases comes about because of the strengthening of systolic pulses due to major artery hardening that generates intense CSF extensional flow stress. Such stress provides the activation energy needed to induce conformational changes of both Aβ and tau within the lower brain and brainstem region, producing unique neurotoxic oligomer molecule conformations that induce AD.

scholarly journals ATN incorporating cerebrospinal fluid neurofilament light chain detects frontotemporal lobar degeneration

2020 ◽  
Author(s):  
Katheryn A.Q. Cousins ◽  
Jeffrey S. Phillips ◽  
David J. Irwin ◽  
Edward B. Lee ◽  
David A. Wolk ◽  
...  
Keyword(s):  
Cerebrospinal Fluid ◽  
Light Chain ◽  
Frontotemporal Lobar Degeneration ◽  
Neurofilament Light Chain ◽  
Neurofilament Light

scholarly journals Cerebrospinal Fluid Biomarkers of Alzheimer’s Disease: Current Evidence and Future Perspectives

2021 ◽  
Vol 11 (2) ◽  
pp. 215
Author(s):  
Donovan A. McGrowder ◽  
Fabian Miller ◽  
Kurt Vaz ◽  
Chukwuemeka Nwokocha ◽  
Cameil Wilson-Clarke ◽  
...  
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Cerebrospinal Fluid ◽  
Late Onset ◽  
Amyloid Β ◽  
Current Evidence ◽  
Csf Biomarkers ◽  
Diagnostic Efficacy ◽  
Neurofilament Light ◽  
New Biomarkers

Alzheimer’s disease is a progressive, clinically heterogeneous, and particularly complex neurodegenerative disease characterized by a decline in cognition. Over the last two decades, there has been significant growth in the investigation of cerebrospinal fluid (CSF) biomarkers for Alzheimer’s disease. This review presents current evidence from many clinical neurochemical studies, with findings that attest to the efficacy of existing core CSF biomarkers such as total tau, phosphorylated tau, and amyloid-β (Aβ42), which diagnose Alzheimer’s disease in the early and dementia stages of the disorder. The heterogeneity of the pathophysiology of the late-onset disease warrants the growth of the Alzheimer’s disease CSF biomarker toolbox; more biomarkers showing other aspects of the disease mechanism are needed. This review focuses on new biomarkers that track Alzheimer’s disease pathology, such as those that assess neuronal injury (VILIP-1 and neurofilament light), neuroinflammation (sTREM2, YKL-40, osteopontin, GFAP, progranulin, and MCP-1), synaptic dysfunction (SNAP-25 and GAP-43), vascular dysregulation (hFABP), as well as CSF α-synuclein levels and TDP-43 pathology. Some of these biomarkers are promising candidates as they are specific and predict future rates of cognitive decline. Findings from the combinations of subclasses of new Alzheimer’s disease biomarkers that improve their diagnostic efficacy in detecting associated pathological changes are also presented.

Sign in / Sign up

Export Citation Format

Share Document