Performance of Fully Automated Plasma Assays as Screening Tests for Alzheimer Disease–Related β-Amyloid Status

Palmqvist, Sebastian; Bateman, Randall J.; Stomrud, Erik; Zetterberg, Henrik; Karl, J. Philip; Zink, Katharina; Bittner, Tobias; Mattsson, Niklas; Eichenlaub, Udo; Blennow, Kaj; Hansson, Oskar

doi:10.1001/jamaneurol.2019.1632

Cited by 340 publications

(388 citation statements)

References 51 publications

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“…We acknowledge that cross‐validation in external cohorts is essential. Of note, our results do not stand alone; multiple recent studies using highly sensitive immunoassays for blood‐based amyloid beta quantification showed capability to discriminate between amyloid‐positive and amyloid‐negative cognitively normal individuals, with or without subjective cognitive complaints, providing independent support for our findings. Moreover, in our article we not only investigated the association of plasma amyloid and CSF amyloid, but showed that low plasma amyloid levels are related to a higher risk of subsequent clinical disease progression to mild cognitive impairment or dementia.…”

supporting

confidence: 71%

Reply to “Usefulness of Plasma Amyloid as Prescreener of the Earliest Alzheimer Pathological Changes Depends on the Study Population”

Verberk

Teunissen

Flier

2019

Annals of Neurology

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supporting

confidence: 71%

Reply to “Usefulness of Plasma Amyloid as Prescreener of the Earliest Alzheimer Pathological Changes Depends on the Study Population”

Verberk

Teunissen

Flier

2019

Annals of Neurology

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“…Blood samples were collected at the same time as CSF samples and handled according to a structured pre‐analytical protocol (Palmqvist et al , ). Plasma Aβ42, Aβ40, and T‐tau concentrations were measured using the Elecsys ® immunoassays on a cobas e ® 601 analyzer (Palmqvist et al , ). NfL was analyzed as previously described (Hansson et al , ).…”

Section: Methodsmentioning

confidence: 99%

Cerebrospinal fluid and plasma biomarker trajectories with increasing amyloid deposition in Alzheimer's disease

et al. 2019

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Failures in Alzheimer's disease (AD) drug trials highlight the need to further explore disease mechanisms and alterations of biomarkers during the development of AD. Using cross‐sectional data from 377 participants in the BioFINDER study, we examined seven cerebrospinal fluid (CSF) and six plasma biomarkers in relation to β‐amyloid (Aβ) PET uptake to understand their evolution during AD. In CSF, Aβ42 changed first, closely followed by Aβ42/Aβ40, phosphorylated‐tau (P‐tau), and total‐tau (T‐tau). CSF neurogranin, YKL‐40, and neurofilament light increased after the point of Aβ PET positivity. The findings were replicated using Aβ42, Aβ40, P‐tau, and T‐tau assays from five different manufacturers. Changes were seen approximately simultaneously for CSF and plasma biomarkers. Overall, plasma biomarkers had smaller dynamic ranges, except for CSF and plasma P‐tau which were similar. In conclusion, using state‐of‐the‐art biomarkers, we identified the first changes in Aβ, closely followed by soluble tau. Only after Aβ PET became abnormal, biomarkers of neuroinflammation, synaptic dysfunction, and neurodegeneration were altered. These findings lend in vivo support of the amyloid cascade hypotheses in humans.

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“…Recent advancements in proteomic assays have demonstrated the potential use of plasma Aβ to identify brain Aβ‐positive individuals with moderate‐to‐high accuracy [4–8]. The measurement of T‐tau in plasma has limited diagnostic value, albeit being slightly but significantly increased in patients with AD [9] but promising data are emerging on P‐tau [10].…”

Section: Introductionmentioning

confidence: 99%

“…Recent advancements in proteomic assays have demonstrated the potential use of plasma Ab to identify brain Abpositive individuals with moderate-to-high accuracy [4][5][6][7][8].…”

Section: Introductionmentioning

confidence: 99%

Plasma neurofilament light associates with Alzheimer's disease metabolic decline in amyloid‐positive individuals

Benedet

Ashton

Leuzy

et al. 2019

Alz & Dem Diag Ass & Dis Mo

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Introduction Neurofilament light chain (NfL) is a promising blood biomarker to detect neurodegeneration in Alzheimer's disease (AD) and other brain disorders. However, there are limited reports of how longitudinal NfL relates to imaging biomarkers. We herein investigated the relationship between blood NfL and brain metabolism in AD. Methods Voxelwise regression models tested the cross‐sectional association between [18F]fluorodeoxyglucose ([18F]FDG) and both plasma and cerebrospinal fluid NfL in cognitively impaired and unimpaired subjects. Linear mixed models were also used to test the longitudinal association between NfL and [18F]FDG in amyloid positive (Aβ+) and negative (Aβ−) subjects. Results Higher concentrations of plasma and cerebrospinal fluid NfL were associated with reduced [18F]FDG uptake in correspondent brain regions. In Aβ+ participants, NfL associates with hypometabolism in AD‐vulnerable regions. Longitudinal changes in the association [18F]FDG‐NfL were confined to cognitively impaired Aβ+ individuals. Discussion These findings indicate that plasma NfL is a proxy for neurodegeneration in AD‐related regions in Aβ+ subjects.

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Performance of Fully Automated Plasma Assays as Screening Tests for Alzheimer Disease–Related β-Amyloid Status

Cited by 340 publications

References 51 publications

Reply to “Usefulness of Plasma Amyloid as Prescreener of the Earliest Alzheimer Pathological Changes Depends on the Study Population”

Reply to “Usefulness of Plasma Amyloid as Prescreener of the Earliest Alzheimer Pathological Changes Depends on the Study Population”

Cerebrospinal fluid and plasma biomarker trajectories with increasing amyloid deposition in Alzheimer's disease

Plasma neurofilament light associates with Alzheimer's disease metabolic decline in amyloid‐positive individuals

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