Plasma Amyloid as Prescreener for the Earliest Alzheimer Pathological Changes

Objective We investigated the association of plasma amyloid beta (Abeta)40, Abeta42, and total tau (tTau) with the presence of Alzheimer pathological changes in cognitively normal individuals with subjective cognitive decline (SCD). Methods We included 248 subjects with SCD (61 ± 9 years, 42% female...

Full description

Saved in:
Bibliographic Details
Published in:Annals of neurology 2018-11, Vol.84 (5), p.648-658
Main Authors: Verberk, Inge M. W., Slot, Rosalinde E., Verfaillie, Sander C. J., Heijst, Hans, Prins, Niels D., van Berckel, Bart N. M., Scheltens, Philip, Teunissen, Charlotte E., van der Flier, Wiesje M.
Format: Article
Language:English
Subjects:
Aged
Alzheimer Disease - blood
Alzheimer Disease - diagnosis
Alzheimer Disease - pathology
Amyloid beta-Peptides - blood
Apolipoprotein E
Biomarkers - blood
Cerebrospinal fluid
Cognitive ability
Cognitive Dysfunction - blood
Cognitive Dysfunction - diagnosis
Confidence intervals
Dementia
Dementia disorders
Early Diagnosis
Female
Humans
Male
Middle Aged
Plasma
Plasma levels
Positron emission
Positron emission tomography
Regression analysis
Sensitivity and Specificity
Statistical analysis
Statistical models
Tau protein
Tomography
Citations: Items that cite this one
Online Access:Get full text
Tags: Add Tag
No Tags, Be the first to tag this record!
Description
Summary:Objective We investigated the association of plasma amyloid beta (Abeta)40, Abeta42, and total tau (tTau) with the presence of Alzheimer pathological changes in cognitively normal individuals with subjective cognitive decline (SCD). Methods We included 248 subjects with SCD (61 ± 9 years, 42% female, Mini‐Mental State Examination = 28 ± 2) from the SCIENCe project and Amsterdam Dementia Cohort. Subjects were dichotomized as amyloid abnormal by cerebrospinal fluid (CSF) and positron emission tomography (PET). Baseline plasma Abeta40, Abeta42, and tTau were measured using Simoa technology. Associations between plasma levels and amyloid status were assessed using logistic regression analyses and receiver operating characteristic analyses. Association of plasma levels with risk of clinical progression to mild cognitive impairment (MCI) or dementia was assessed using Cox proportional hazard models. Results Fifty‐seven (23%) subjects were CSF‐amyloid abnormal. Plasma Abeta42/Abeta40 ratio and plasma Abeta42 alone, but not tTau, identified abnormal CSF‐amyloid status (plasma ratio: area under the curve [AUC] = 77%, 95% confidence interval [CI] = 69–84%; plasma Abeta42: AUC = 66%, 95% CI: 58–74%). Combining plasma ratio with age and apolipoprotein E resulted in AUC = 83% (95% CI = 77–89%). The Youden cutoff of the plasma ratio gave a sensitivity of 76% and specificity of 75%, and applying this as a prescreener would reduce the number of lumbar punctures by 51%. Using PET as outcome, a comparable reduction in number of PET scans would be achieved when applying the plasma ratio as prescreener. In addition, low plasma ratio was associated with clinical progression to MCI or dementia (hazard ratio = 2.0, 95% CI = 1.4–2.3). Interpretation Plasma Abeta42/Abeta40 ratio has potential as a prescreener to identify Alzheimer pathological changes in cognitively normal individuals with SCD. Ann Neurol 2018;84:656–666
ISSN:0364-5134
1531-8249
DOI:10.1002/ana.25334