Comparison of plasma and <scp>CSF</scp> biomarkers in predicting cognitive decline

Aschenbrenner, Andrew J.; Li, Yan; Henson, Rachel L.; Volluz, Katherine; Hassenstab, Jason; Verghese, Philip B.; West, Tim; Meyer, Matthew R.; Kirmess, Kristopher M.; Xiong, Chengjie; Holtzman, David M.; Morris, John C.; Bateman, Randall J.; Schindler, Suzanne E.

doi:10.1002/acn3.51670

Cited by 28 publications

(26 citation statements)

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“…In general, the simultaneous consideration of several plasma biomarkers levels could improve the early and specific diagnosis approach. So, some biomarkers panels have been evaluated in previous studies [ 63 , 64 , 65 , 66 ], showing some advantages in potential AD diagnosis. In fact, the use of only one plasma biomarker shows some limitations (non-specificity for AD, not enough sensitivity identifying AD stages).…”

Section: Discussionmentioning

confidence: 99%

Assessment of Plasma and Cerebrospinal Fluid Biomarkers in Different Stages of Alzheimer’s Disease and Frontotemporal Dementia

Álvarez-Sánchez

Peña-Bautista²,

Ferré-González³

et al. 2023

IJMS

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Alzheimer’s disease (AD) is the primary type of dementia, followed by frontotemporal lobar degeneration (FTLD). They share some clinical characteristics, mainly at the early stages. So, the identification of early, specific, and minimally invasive biomarkers is required. In this study, some plasma biomarkers (Amyloid β42, p-Tau181, t-Tau, neurofilament light (NfL), TAR DNA-binding protein 43 (TDP-43)) were determined by single molecule array technology (SIMOA®) in control subjects (n = 22), mild cognitive impairment due to AD (MCI-AD, n = 33), mild dementia due to AD (n = 12), and FTLD (n = 11) patients. The correlations between plasma and cerebrospinal fluid (CSF) levels and the accuracy of plasma biomarkers for AD early diagnosis and discriminating from FTLD were analyzed. As result, plasma p-Tau181 and NfL levels correlated with the corresponding CSF levels. Additionally, plasma p-Tau181 showed good accuracy for distinguishing between the controls and AD, as well as discriminating between AD and FTLD. Moreover, plasma NfL could discriminate dementia-AD vs. controls, FTLD vs. controls, and MCI-AD vs. dementia-AD. Therefore, the determination of these biomarkers in plasma is potentially helpful in AD spectrum diagnosis, but also discriminating from FTLD. In addition, the accessibility of these potential early and specific biomarkers may be useful for AD screening protocols in the future.

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Section: Discussionmentioning

confidence: 99%

Assessment of Plasma and Cerebrospinal Fluid Biomarkers in Different Stages of Alzheimer’s Disease and Frontotemporal Dementia

Álvarez-Sánchez

Peña-Bautista²,

Ferré-González³

et al. 2023

IJMS

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“…NfL and YKL‐40 were measured with plate‐based commercial Enzyme‐Linked Immunosorbent Assays (ELISAs) manufactured by Uman Diagnostics and Quidel, respectively, and as previously described 22,23 . Measuring range and control values are in supplemental materials (Table S12, S13, and S14).…”

Section: Methodsmentioning

confidence: 99%

Cerebrospinal fluid biomarkers in the Longitudinal Early‐onset Alzheimer's Disease Study

Dage,

Eloyan,

Thangarajah

et al. 2023

Alzheimer's & Dementia

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IntroductionOne goal of the Longitudinal Early Onset Alzheimer's Disease Study (LEADS) is to define the fluid biomarker characteristics of early‐onset Alzheimer's disease (EOAD).MethodsCerebrospinal fluid (CSF) concentrations of Aβ1‐40, Aβ1‐42, total tau (tTau), pTau181, VILIP‐1, SNAP‐25, neurogranin (Ng), neurofilament light chain (NfL), and YKL‐40 were measured by immunoassay in 165 LEADS participants. The associations of biomarker concentrations with diagnostic group and standard cognitive tests were evaluated.ResultsBiomarkers were correlated with one another. Levels of CSF Aβ42/40, pTau181, tTau, SNAP‐25, and Ng in EOAD differed significantly from cognitively normal and early‐onset non‐AD dementia; NfL, YKL‐40, and VILIP‐1 did not. Across groups, all biomarkers except SNAP‐25 were correlated with cognition. Within the EOAD group, Aβ42/40, NfL, Ng, and SNAP‐25 were correlated with at least one cognitive measure.DiscussionThis study provides a comprehensive analysis of CSF biomarkers in sporadic EOAD that can inform EOAD clinical trial design.

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“…33 Plasma NfL and GFAP were measured via Quanterix Neuro 2-Plex B Advantage assay kits on a SIMOA HD-X analyzer at Washington University according to manufacturer's specifications. 34 CSF Aβ42, Aβ40, p-tau181, and total tau (t-tau) concentrations were measured with an automated immunoassay platform (LUMIPULSE G1200, Fujirebio) according to manufacturer's specifications. 12 CSF pT181/T181, pT205/T205, pT217/T217, and pT231/231 were measured via an immunoprecipitation-mass spectrometry assay.…”

Section: Plasma and Csf Assaysmentioning

confidence: 99%

“…26 CSF NfL and YKL-40 were measured with commercial ELISAs, manufactured by Uman Diagnostics and Quidel, respectively. 34,35 Amyloid PET and Structural Brain MRI Participants underwent amyloid PET using 11 C-Pittsburgh Compound B (PiB) in coordination with a 3 Tesla structural MRI scan. T 1 -weighted MRIs were processed using Freesurfer 5.3 to generate regions of interest used for the processing of PET data.…”

Section: Plasma and Csf Assaysmentioning

confidence: 99%

Timing of Biomarker Changes in Sporadic Alzheimer's Disease in Estimated Years from Symptom Onset

Li,

Yen,

Hendrix

et al. 2024

Annals of Neurology

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ObjectiveA clock relating amyloid positron emission tomography (PET) to time was used to estimate the timing of biomarker changes in sporadic Alzheimer disease (AD).MethodsResearch participants were included who underwent cerebrospinal fluid (CSF) collection within 2 years of amyloid PET. The ages at amyloid onset and AD symptom onset were estimated for each individual. The timing of change for plasma, CSF, imaging, and cognitive measures was calculated by comparing restricted cubic splines of cross‐sectional data from the amyloid PET positive and negative groups.ResultsThe amyloid PET positive sub‐cohort (n = 118) had an average age of 70.4 ± 7.4 years (mean ± standard deviation) and 16% were cognitively impaired. The amyloid PET negative sub‐cohort (n = 277) included individuals with low levels of amyloid plaque burden at all scans who were cognitively unimpaired at the time of the scans. Biomarker changes were detected 15–19 years before estimated symptom onset for CSF Aβ42/Aβ40, plasma Aβ42/Aβ40, CSF pT217/T217, and amyloid PET; 12–14 years before estimated symptom onset for plasma pT217/T217, CSF neurogranin, CSF SNAP‐25, CSF sTREM2, plasma GFAP, and plasma NfL; and 7–9 years before estimated symptom onset for CSF pT205/T205, CSF YKL‐40, hippocampal volumes, and cognitive measures.InterpretationThe use of an amyloid clock enabled visualization and analysis of biomarker changes as a function of estimated years from symptom onset in sporadic AD. This study demonstrates that estimated years from symptom onset based on an amyloid clock can be used as a continuous staging measure for sporadic AD and aligns with findings in autosomal dominant AD. ANN NEUROL 2024

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Comparison of plasma and CSF biomarkers in predicting cognitive decline

Cited by 28 publications

References 50 publications

Assessment of Plasma and Cerebrospinal Fluid Biomarkers in Different Stages of Alzheimer’s Disease and Frontotemporal Dementia

Assessment of Plasma and Cerebrospinal Fluid Biomarkers in Different Stages of Alzheimer’s Disease and Frontotemporal Dementia

Cerebrospinal fluid biomarkers in the Longitudinal Early‐onset Alzheimer's Disease Study

Timing of Biomarker Changes in Sporadic Alzheimer's Disease in Estimated Years from Symptom Onset

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