Immunity and amyloid beta, total tau and neurofilament light chain: Findings from a community‐based cohort study

Abstract Background Neurofilament light chain (NfL) is a promising biomarker of neurodegeneration in the cerebrospinal fluid and blood. This study investigated the presence of NfL in the vitreous humor and its associations with amyloid beta, tau, inflammatory cytokines and vascular proteins, apolipoprotein E (APOE) genotypes, Mini-Mental State Examination (MMSE) scores, systemic disease, and ophthalmic diseases. Methods This is a single-site, prospective, cross-sectional cohort study. Undiluted vitreous fluid (0.5–1.0 mL) was aspirated during vitrectomy, and whole blood was drawn for APOE genotyping. NfL, amyloid beta (Aβ), total Tau (t-Tau), phosphorylated Tau (p-Tau181), inflammatory cytokines, chemokines, and vascular proteins in the vitreous were quantitatively measured by immunoassay. The main outcome measures were the detection of NfL levels in the vitreous humor and its associations with the aforementioned proteins. Linear regression was used to test the associations of NfL with other proteins, APOE genotypes, MMSE scores, and ophthalmic and systemic diseases after adjustment for age, sex, education level, and other eye diseases. Results NfL was detected in all 77 vitreous samples. NfL was not found to be associated with ophthalmic conditions, APOE genotypes, MMSE scores, or systemic disease (p > 0.05). NfL levels were positively associated with increased vitreous levels of Aβ40 (p = 7.7 × 10−5), Aβ42 (p = 2.8 × 10−4), and t-tau (p = 5.5 × 10−7), but not with p-tau181 (p = 0.53). NfL also had significant associations with inflammatory cytokines such as interleukin-15 (IL-15, p = 5.3 × 10−4), IL-16 (p = 2.2 × 10−4), monocyte chemoattractant protein-1 (MCP1, p = 4.1 × 10−4), and vascular proteins such as vascular endothelial growth factor receptor-1 (VEGFR1, p = 2.9 × 10−6), Vegf-C (p = 8.6 × 10−6), vascular cell adhesion molecule-1 (VCAM-1, p = 5.0 × 10−4), Tie-2 (p = 6.3 × 10−4), and intracellular adhesion molecular-1 (ICAM-1, p = 1.6 × 10−4). Conclusion NfL is detectable in the vitreous humor of the eye and significantly associated with amyloid beta, t-tau, and select inflammatory and vascular proteins in the vitreous. Additionally, NfL was not associated with patients’ clinical eye condition. Our results serve as a foundation for further investigation of NfL in the ocular fluids to inform us about the potential utility of its presence in the eye.

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

Brain Communications ◽

10.1093/braincomms/fcaa054 ◽

2020 ◽

Vol 2 (1) ◽

Cited By ~ 2

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.

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Serum neurofilament light chain in genetic frontotemporal dementia: a longitudinal, multicentre cohort study

The Lancet Neurology ◽

10.1016/s1474-4422(19)30354-0 ◽

2019 ◽

Vol 18 (12) ◽

pp. 1103-1111 ◽

Cited By ~ 27

Author(s):

Emma L van der Ende ◽

Lieke H Meeter ◽

Jackie M Poos ◽

Jessica L Panman ◽

Lize C Jiskoot ◽

...

Keyword(s):

Cohort Study ◽

Frontotemporal Dementia ◽

Light Chain ◽

Neurofilament Light Chain ◽

Neurofilament Light ◽

Multicentre Cohort Study ◽

Multicentre Cohort

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Amyloid-beta modulates the association between neurofilament light chain and brain atrophy in Alzheimer’s disease

Molecular Psychiatry ◽

10.1038/s41380-020-0818-1 ◽

2020 ◽

Author(s):

Min Su Kang ◽

◽

Arturo Aliaga Aliaga ◽

Monica Shin ◽

Sulantha Mathotaarachchi ◽

...

Keyword(s):

Alzheimer’S Disease ◽

Alzheimer's Disease ◽

Amyloid Beta ◽

Light Chain ◽

Brain Atrophy ◽

Neurofilament Light Chain ◽

Neurofilament Light

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

Neurology ◽

10.1212/wnl.0000000000012123 ◽

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.

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

10.21203/rs.3.rs-88939/v1 ◽

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.

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Sleep, 24-h activity rhythms, and plasma markers of neurodegenerative disease

Scientific Reports ◽

10.1038/s41598-020-77830-4 ◽

2020 ◽

Vol 10 (1) ◽

Author(s):

Thom S. Lysen ◽

M. Arfan Ikram ◽

Mohsen Ghanbari ◽

Annemarie I. Luik

Keyword(s):

Neurodegenerative Disease ◽

Light Chain ◽

Multiple Testing ◽

Neuronal Damage ◽

Activity Rhythm ◽

Neurofilament Light Chain ◽

Neurofilament Light ◽

Activity Rhythms ◽

Total Tau ◽

Β Amyloid

AbstractSleep and 24-h activity rhythm disturbances are associated with development of neurodegenerative diseases and related pathophysiological processes in the brain. We determined the cross-sectional relation of sleep and 24-h activity rhythm disturbances with plasma-based biomarkers that might signal neurodegenerative disease, in 4712 middle-aged and elderly non-demented persons. Sleep and activity rhythms were measured using the Pittsburgh Sleep Quality Index and actigraphy. Simoa assays were used to measure plasma levels of neurofilament light chain, and additionally β-amyloid 40, β-amyloid 42, and total-tau. We used linear regression, adjusting for relevant confounders, and corrected for multiple testing. We found no associations of self-rated sleep, actigraphy-estimated sleep and 24-h activity rhythms with neurofilament light chain after confounder adjustment and correction for multiple testing, except for a non-linear association of self-rated time in bed with neurofilament light chain (P = 2.5*10−4). Similarly, we observed no significant associations with β-amyloid 40, β-amyloid 42, and total-tau after multiple testing correction. We conclude that sleep and 24-h activity rhythm disturbances were not consistently associated with neuronal damage as indicated by plasma neurofilament light chain in this population-based sample middle-aged and elderly non-demented persons. Further studies are needed to determine the associations of sleep and 24-h activity rhythm disturbances with NfL-related neuronal damage.

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