Temporal Correlation of CSF and Neuroimaging in the Amyloid-Tau-Neurodegeneration Model of Alzheimer Disease

Neurology ◽  
2021 ◽  
Author(s):  
Anna H. Boerwinkle ◽  
Julie K. Wisch ◽  
Charles D. Chen ◽  
Brian A. Gordon ◽  
Omar Hameed Butt ◽  
...  
Keyword(s):  
Alzheimer Disease ◽  
Cortical Thickness ◽  
Light Chain ◽  
Amyloid Β ◽  
Time Interval ◽  
Phosphorylated Tau ◽  
Neurofilament Light Chain ◽  
Neurofilament Light ◽  
Total Tau ◽  
Maximal Correlation

Objective:Temporal correlations between CSF and neuroimaging (PET and MRI) measures of amyloid, tau, and neurodegeneration were evaluated in relation to Alzheimer disease (AD) progression.Methods:Three hundred seventy-one cognitively unimpaired and impaired participants enrolled in longitudinal studies of AD had both CSF (amyloid-β42, phosphorylated tau181, total tau, and neurofilament light chain) and neuroimaging (PiB PET, flortaucipir PET, and structural MRI) measures. The pairwise time interval between CSF and neuroimaging measures was binned into two year periods. Spearman correlations identified the time bin when CSF and neuroimaging measures most strongly correlated. CSF and neuroimaging measures were then binarized as biomarker-positive or biomarker-negative using Gaussian mixture modelling. Cohen’s kappa coefficient identified the time bin when CSF measures best agreed with corresponding neuroimaging measures when determining amyloid, tau, and neurodegeneration biomarker positivity.Results:CSF amyloid-β42 and PiB PET showed maximal correlation when collected within six years of each other (R ≈ -0.5). CSF phosphorylated tau181 and flortaucipir PET showed maximal correlation when CSF was collected four to eight years prior to PET (R ≈ 0.4). CSF neurofilament light chain and cortical thickness showed low correlation, regardless of time interval (Ravg ≈ -0.3). Similarly, CSF total tau and cortical thickness had low correlation, regardless of time interval (Ravg < -0.2).Conclusions:CSF amyloid-β42 and PiB PET best agree when acquired in close temporal proximity, whereas CSF phosphorylated tau precedes flortaucipir PET by four to eight years. CSF and neuroimaging measures of neurodegeneration have low correspondence and are not interchangeable at any time interval.

scholarly journals In the blood: biomarkers for amyloid pathology and neurodegeneration in Alzheimer’s disease

2020 ◽  
Vol 2 (1) ◽  
Author(s):  
Jamie Toombs ◽  
Henrik Zetterberg
Keyword(s):  
Light Chain ◽  
Amyloid Β ◽  
Population Based ◽  
Blood Biomarkers ◽  
Neurofilament Light Chain ◽  
Population Based Study ◽  
Neurofilament Light ◽  
Total Tau ◽  
Amyloid Pathology ◽  
Relationship Of

This scientific commentary refers to ‘Plasma total-tau, neurofilament light chain and amyloid-β levels and risk of dementia: a population-based study’ by de Wolf et al. (https://doi.org/10.1093/brain/awaa054), and ‘Relationship of amyloid-b1–42 in blood and brain amyloid: Ginkgo Evaluation of Memory Study’ by Lopez et al. (https://doi.org/10.1093/braincomms/fcz038), two papers that illustrate these latest developments.

scholarly journals Performance of Plasma Amyloid β, Total Tau and Neurofilament Light Chain Levels for Alzheimer’s Disease Identification

2020 ◽  
Author(s):  
Bin Jiao ◽  
Hui Liu ◽  
Lina Guo ◽  
Xinxin Liao ◽  
Yafang Zhou ◽  
...  
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Light Chain ◽  
Amyloid Β ◽  
Amyloid Pet ◽  
Neurofilament Light Chain ◽  
Neurofilament Light ◽  
Plasma Biomarkers ◽  
Total Tau ◽  
T Tau

Abstract BackgroundRobust studies have focused on blood-based biomarkers for diagnosis of Alzheimer’s disease (AD), while the results were still controversary and failed verified in different cohorts. The aim of this study was to detect the levels of plasma amyloid β (Aβ), total tau (t-tau), and neurofilament light chain (NfL) in patients with AD and cognitive normal (CN) subjects, and clarify their associations with Aβ, t-tau, and phosphorylated tau (p-tau) in cerebrospinal fluid (CSF) as well as brain amyloid PET, and calculate the diagnostic efficiency of these characteristics regarding AD.Methods Plasma Aβ42, Aβ40, t-tau and NfL levels were detected by single-molecule array (Simoa) in 379 AD patients and 153 CN subjects. Additionally, lumbar puncture was conducted in 125 AD patients to detect Aβ42, Aβ40, t-tau, and p-tau levels. Brain amyloid PET was performed in 52 AD patients to identify brain amyloid deposition levels. Correlation analysis were performed between plasma biomarkers and typical biomarkers of AD, including CSF core biomarkers and amyloid PET burden. Finally, the diagnostic value of plasma biomarkers was further assessed by receiver operating characteristic (ROC) curve.ResultsCompared with the CN group, plasma Aβ42 and Aβ42/Aβ40 levels were significantly lower in AD patients, while Aβ40, t-tau and NfL levels were higher in AD patients. Among the AD patients, plasma Aβ42 was positively correlated with CSF Aβ42 (r = 0.195, p = 0.03) and Aβ42/Aβ40 (r = 0.208, p = 0.04). Moreover, plasma NfL was positively correlated with age, disease course and severity. The diagnostic model with combined plasma Aβ42, t-tau, and NfL levels controlled for age and APOE genotype showed the best performance to identify AD (area under the curve (AUC) = 0.88, sensitivity = 82.84%, specificity = 81.69%, cutoff value = 0.64).ConclusionsTrends revealed by core biomarkers were generally consistent in AD patients’ plasma and CSF. Combining plasma biomarkers can provide comparatively high AD diagnostic performance.

scholarly journals Performance of Plasma Amyloid β, Total Tau, and Neurofilament Light Chain in the Identification of Probable Alzheimer's Disease in South China

2021 ◽  
Vol 13 ◽  
Author(s):  
Bin Jiao ◽  
Hui Liu ◽  
Lina Guo ◽  
Xinxin Liao ◽  
Yafang Zhou ◽  
...  
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Correlation Analysis ◽  
Light Chain ◽  
Amyloid Β ◽  
Neurofilament Light Chain ◽  
Neurofilament Light ◽  
Plasma Biomarkers ◽  
Total Tau ◽  
T Tau

Background: Alzheimer's disease (AD) is the most common type of dementia and has no effective treatment to date. It is essential to develop a minimally invasive blood-based biomarker as a tool for screening the general population, but the efficacy remains controversial. This cross-sectional study aimed to evaluate the ability of plasma biomarkers, including amyloid β (Aβ), total tau (t-tau), and neurofilament light chain (NfL), to detect probable AD in the South Chinese population.Methods: A total of 277 patients with a clinical diagnosis of probable AD and 153 healthy controls with normal cognitive function (CN) were enrolled in this study. The levels of plasma Aβ42, Aβ40, t-tau, and NfL were detected using ultra-sensitive immune-based assays (SIMOA). Lumbar puncture was conducted in 89 patients with AD to detect Aβ42, Aβ40, t-tau, and phosphorylated (p)-tau levels in the cerebrospinal fluid (CSF) and to evaluate the consistency between plasma and CSF biomarkers through correlation analysis. Finally, the diagnostic value of plasma biomarkers was further assessed by constructing a receiver operating characteristic (ROC) curve.Results: After adjusting for age, sex, and the apolipoprotein E (APOE) alleles, compared to the CN group, the plasma t-tau, and NfL were significantly increased in the AD group (p &lt; 0.01, Bonferroni correction). Correlation analysis showed that only the plasma t-tau level was positively correlated with the CSF t-tau levels (r = 0.319, p = 0.003). The diagnostic model combining plasma t-tau and NfL levels, and age, sex, and APOE alleles, showed the best performance for the identification of probable AD [area under the curve (AUC) = 0.89, sensitivity = 82.31%, specificity = 83.66%].Conclusion: Blood biomarkers can effectively distinguish patients with probable AD from controls and may be a non-invasive and efficient method for AD pre-screening.

Association of Plasma Neurofilament Light Chain with Neocortical Amyloid-β Load and Cognitive Performance in Cognitively Normal Elderly Participants

2018 ◽  
Vol 63 (2) ◽  
pp. 479-487 ◽  
Author(s):  
Pratishtha Chatterjee ◽  
Kathryn Goozee ◽  
Hamid R. Sohrabi ◽  
Kaikai Shen ◽  
Tejal Shah ◽  
...  
Keyword(s):  
Cognitive Performance ◽  
Light Chain ◽  
Amyloid Β ◽  
Neurofilament Light Chain ◽  
Neurofilament Light ◽  
Cognitively Normal

scholarly journals Untangling the association of amyloid-β and tau with synaptic and axonal loss in Alzheimer’s disease

Brain ◽  
2020 ◽  
Author(s):  
Joana B Pereira ◽  
Shorena Janelidze ◽  
Rik Ossenkoppele ◽  
Hlin Kvartsberg ◽  
Ann Brinkmalm ◽  
...  
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Light Chain ◽  
Diffusion Tensor ◽  
Amyloid Β ◽  
Synaptic Function ◽  
Dependent Manner ◽  
Tau Pathology ◽  
Neurofilament Light Chain ◽  
Neurofilament Light

Abstract It is currently unclear how amyloid-β and tau deposition are linked to changes in synaptic function and axonal structure over the course of Alzheimer’s disease. Here, we assessed these relationships by measuring presynaptic (synaptosomal-associated protein 25, SNAP25; growth-associated protein 43, GAP43), postsynaptic (neurogranin, NRGN) and axonal (neurofilament light chain) markers in the CSF of individuals with varying levels of amyloid-β and tau pathology based on 18F-flutemetamol PET and 18F-flortaucipir PET. In addition, we explored the relationships between synaptic and axonal markers with cognition as well as functional and anatomical brain connectivity markers derived from resting-state functional MRI and diffusion tensor imaging. We found that the presynaptic and postsynaptic markers SNAP25, GAP43 and NRGN are elevated in early Alzheimer’s disease i.e. in amyloid-β-positive individuals without evidence of tau pathology. These markers were associated with greater amyloid-β pathology, worse memory and functional changes in the default mode network. In contrast, neurofilament light chain was abnormal in later disease stages, i.e. in individuals with both amyloid-β and tau pathology, and correlated with more tau and worse global cognition. Altogether, these findings support the hypothesis that amyloid-β and tau might have differential downstream effects on synaptic and axonal function in a stage-dependent manner, with amyloid-related synaptic changes occurring first, followed by tau-related axonal degeneration.

Plasma amyloid beta, neurofilament light chain, and total tau in the Systolic Blood Pressure Intervention Trial (SPRINT)

2021 ◽  
Author(s):  
Nicholas M. Pajewski ◽  
Fanny M. Elahi ◽  
Manjula Kurella Tamura ◽  
Jason D. Hinman ◽  
Ilya M. Nasrallah ◽  
...  
Keyword(s):  
Blood Pressure ◽  
Systolic Blood Pressure ◽  
Amyloid Beta ◽  
Light Chain ◽  
Intervention Trial ◽  
Neurofilament Light Chain ◽  
Neurofilament Light ◽  
Total Tau
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