Plasma Amyloid as Prescreener for the Earliest Alzheimer Pathological Changes

Abstract

ObjectiveWe 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).MethodsWe 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.ResultsFifty‐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).InterpretationPlasma 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

Aβ and tau structure‐based biomarkers for a blood‐ and CSF‐based two‐step recruitment strategy to identify patients with dementia due to Alzheimer's disease

“…In clinical studies focusing on Aβ‐PET–positive severe AD cases, both approaches revealed an accuracy of 85‐90% with the Aβ‐PET status. Most recently, Verberk et al [16] focused on the identification of cognitively normal individuals with subjective cognitive decline, which converted to MCI or AD over years, by measuring the A42/40 ratio in blood plasma using the Single Molecule Array technology. This approach resulted in the Amsterdam study in a diagnostic accuracy of 76% [16].…”

“…Most recently, Verberk et al [16] focused on the identification of cognitively normal individuals with subjective cognitive decline, which converted to MCI or AD over years, by measuring the A42/40 ratio in blood plasma using the Single Molecule Array technology. This approach resulted in the Amsterdam study in a diagnostic accuracy of 76% [16]. All technologies may be applied in combination to receive a powerful solely blood‐based AD recruitment platform.

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“…using the Single Molecule Array technology. This approach resulted in the Amsterdam study in a diagnostic accuracy of 76% [16]. All technologies may be applied in combination to receive a powerful solely blood-based AD recruitment platform.…”

Usefulness of Plasma Amyloid as a Prescreener for the Earliest Alzheimer Pathological Changes Depends on the Study Population

“…Recently, Verberk et al showed that plasma Aβ42/Aβ40 ratio has potential to identify Alzheimer pathological changes in subjects with subjective memory decline . Furthermore, the inclusion of age and APOEε4 carriership in their multivariate model improved the likelihood of identification.…”

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

“…We thank Prins et al for applying the methods of our article on “Plasma Amyloid as Prescreener for the Earliest Alzheimer Pathological Changes” to their research. Designing prescreening tools for amyloid positivity will ultimately facilitate recruitment of cognitively normal participants for Alzheimer disease clinical trials.…”