Amyloid β concentrations and stable isotope labeling kinetics of human plasma specific to central nervous system amyloidosis

Ovod, Vitaliy; Ramsey, Kara N.; Mawuenyega, Kwasi G.; Bollinger, Jim G.; Hicks, Terry J.; Schneider, Theresa; Sullivan, Melissa; Paumier, Katrina L.; Holtzman, David M.; Morris, John C.; Benzinger, Tammie L.S.; Fagan, Anne M.; Patterson, Bruce W.; Bateman, Randall J.

doi:10.1016/j.jalz.2017.06.2266

Alzheimer's & Dementia

2017

DOI: 10.1016/j.jalz.2017.06.2266

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Amyloid β concentrations and stable isotope labeling kinetics of human plasma specific to central nervous system amyloidosis

Vitaliy Ovod

¹

,

Kara N. Ramsey

²

,

Kwasi G. Mawuenyega

³

et al.

Abstract: INTRODUCTION CSF analysis and other measurements of amyloidosis, such as amyloid-binding positron emission tomography (PET) studies, are limited by cost and availability. There is a need for a more practical Aβ biomarker for central nervous system (CNS) amyloid deposition. METHODS We adapted our previously reported Stable Isotope Labeling Kinetics (SILK) protocol to analyze the turnover kinetics and concentrations of Aβ38, Aβ40, and Aβ42 in human plasma. RESULTS Aβ isoforms have a half-life of approximatel… Show more

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Cited by 572 publications

(622 citation statements)

References 19 publications

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“…Taken together, the observations from this study suggest that pre-enrichment of Aβ peptides from blood plasma by immunoprecipitation with an antibody against the Aβ N-terminus and in the presence of detergents can substantially facilitate the measurement of specific Aβ variants by a commercially available multiplex immunoassay. Furthermore, our findings support the results of two recent IP-MS studies reporting highly accurate prediction of cerebral amyloid pathology by the blood plasma ratios Aβ42/Aβ40 [ 6 ] and Aβ1–40/Aβ1–42 [ 7 ]. Major limitations of our current study include the small sample size, the need for assay standardization and automatization of manual steps, and the need for inclusion of reference material for normalization between assay plates and experiments.…”

Section: Resultssupporting

confidence: 90%

“…Our findings are in agreement with some previous reports suggesting that a low Aβ42/Aβ40 ratio and/or a low Aβ42 level in plasma represent candidate biomarkers of neuropathological changes related to AD [ 6 , 11 , 24 , 26 – 29 ]. However, this is not supported by several other studies [ 25 , 30 – 32 ].…”

Section: Discussionsupporting

confidence: 93%

See 1 more Smart Citation

A two-step immunoassay for the simultaneous assessment of Aβ38, Aβ40 and Aβ42 in human blood plasma supports the Aβ42/Aβ40 ratio as a promising biomarker candidate of Alzheimer’s disease

Shahpasand‐Kroner

¹

,

Klafki

²

,

Bauer

³

et al. 2018

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Exaggerated anticipatory anxiety is common in social anxiety disorder (SAD). Neuroimaging studies have revealed altered neural activity in response to social stimuli in SAD, but fewer studies have examined neural activity during anticipation of feared social stimuli in SAD. The current study examined the time course and magnitude of activity in threat processing brain regions during speech anticipation in socially anxious individuals and healthy controls (HC). Method Participants (SAD n = 58; HC n = 16) underwent functional magnetic resonance imaging (fMRI) during which they completed a 90s control anticipation task and 90s speech anticipation task.

show abstract

“…Taken together, the observations from this study suggest that pre-enrichment of Aβ peptides from blood plasma by immunoprecipitation with an antibody against the Aβ N-terminus and in the presence of detergents can substantially facilitate the measurement of specific Aβ variants by a commercially available multiplex immunoassay. Furthermore, our findings support the results of two recent IP-MS studies reporting highly accurate prediction of cerebral amyloid pathology by the blood plasma ratios Aβ42/Aβ40 [ 6 ] and Aβ1–40/Aβ1–42 [ 7 ]. Major limitations of our current study include the small sample size, the need for assay standardization and automatization of manual steps, and the need for inclusion of reference material for normalization between assay plates and experiments.…”

Section: Resultssupporting

confidence: 90%

“…Our findings are in agreement with some previous reports suggesting that a low Aβ42/Aβ40 ratio and/or a low Aβ42 level in plasma represent candidate biomarkers of neuropathological changes related to AD [ 6 , 11 , 24 , 26 – 29 ]. However, this is not supported by several other studies [ 25 , 30 – 32 ].…”

Section: Discussionsupporting

confidence: 93%

A two-step immunoassay for the simultaneous assessment of Aβ38, Aβ40 and Aβ42 in human blood plasma supports the Aβ42/Aβ40 ratio as a promising biomarker candidate of Alzheimer’s disease

Shahpasand‐Kroner

¹

,

Klafki

²

,

Bauer

³

et al. 2018

Get access via publisher Add to dashboard Cite

Exaggerated anticipatory anxiety is common in social anxiety disorder (SAD). Neuroimaging studies have revealed altered neural activity in response to social stimuli in SAD, but fewer studies have examined neural activity during anticipation of feared social stimuli in SAD. The current study examined the time course and magnitude of activity in threat processing brain regions during speech anticipation in socially anxious individuals and healthy controls (HC). Method Participants (SAD n = 58; HC n = 16) underwent functional magnetic resonance imaging (fMRI) during which they completed a 90s control anticipation task and 90s speech anticipation task.

show abstract

“…We found that the median and mean AβX–42/X–40 plasma ratios (measured with mAb 6E10) were decreased by 15–16% in amyloid-positive study participants relative to amyloid-negative subjects. This figure is in reasonable agreement with published observations [ 1 , 2 , 15 ]. The differences in the corresponding median and mean Aβ1–42/1–40 plasma ratios (measured with mAb 3D6) between the amyloid pathology subgroups were 20.86% and 18.34%, respectively, indicating an accentuation of contrast.…”

Section: Discussionsupporting

confidence: 94%

Is plasma amyloid-β 1–42/1–40 a better biomarker for Alzheimer’s disease than AβX–42/X–40?

Klafki

¹

,

Morgado

²

,

Wirths

³

et al. 2022

Fluids Barriers CNS

Get access via publisher Add to dashboard Cite

Exaggerated anticipatory anxiety is common in social anxiety disorder (SAD). Neuroimaging studies have revealed altered neural activity in response to social stimuli in SAD, but fewer studies have examined neural activity during anticipation of feared social stimuli in SAD. The current study examined the time course and magnitude of activity in threat processing brain regions during speech anticipation in socially anxious individuals and healthy controls (HC). Method Participants (SAD n = 58; HC n = 16) underwent functional magnetic resonance imaging (fMRI) during which they completed a 90s control anticipation task and 90s speech anticipation task.

show abstract

“…Average concentrations of plasma Aβ were 329.5 pg/mL for Aβ40 and 48.0 pg/mL for Aβ42 for these 36 individuals, with a standard deviation of 89.4 and 12.8 pg/mL, respectively. The average concentrations of plasma Aβ from this study were similar to what has been reported previously . Furthermore, all individual concentrations were within the linear ranges for our developed assay (Figure b,c).…”

Section: Resultssupporting

confidence: 88%

Multiplex Mass Spectrometry Analysis of Amyloid Proteins in Human Plasma for Alzheimer’s Disease Diagnosis

Ni

¹

,

Jagust

²

,

Wang

³

2021

Get access via publisher Add to dashboard Cite

Exaggerated anticipatory anxiety is common in social anxiety disorder (SAD). Neuroimaging studies have revealed altered neural activity in response to social stimuli in SAD, but fewer studies have examined neural activity during anticipation of feared social stimuli in SAD. The current study examined the time course and magnitude of activity in threat processing brain regions during speech anticipation in socially anxious individuals and healthy controls (HC). Method Participants (SAD n = 58; HC n = 16) underwent functional magnetic resonance imaging (fMRI) during which they completed a 90s control anticipation task and 90s speech anticipation task.

show abstract

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