Plasma amyloid as pre-screener for the earliest Alzheimer's pathological changes

Annals of Neurology
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Verberk IMW, Slot RE, Verfaillie SCJ, Heijst H, Prins ND, van Berckel BNM, Scheltens P, Teunissen CE and Van der Flier WM

Ann Neurol. 2018 Sep 9

DOI: https://doi.org/10.1002/ana.25334

ABSTRACT

Objective

We investigated the association of plasma amyloid beta (Abeta)40, Abeta42 and total tau (tTau) with the presence of Alzheimer's pathological changes in cognitively normal individuals with subjective cognitive decline (SCD).

Methods

We included 248 subjects with SCD (61±9yrs, 42%F, 28±2 MMSE) from the SCIENCe project and Amsterdam Dementia Cohort. Subjects were dichotomized as amyloid abnormal by CSF and 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 ROC analyses. Association of plasma levels with risk of clinical progression to mild cognitive impairment (MCI) or dementia were 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: AUC=77% (95%CI: 69%–84%), plasma Abeta42: AUC=66% (95%CI: 58%–74%)). Combining plasma ratio with age and APOE resulted in AUC=83% (95%CI: 77%–89%). Youden's cut‐off of the plasma ratio gave a sensitivity of 76% and specificity of 75%, and applying this as pre‐screener 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 pre‐screener. In addition, low plasma ratio was associated with clinical progression to MCI or dementia (HR=2.0 (95%CI: 1.4–2.3)).

Interpretation

Plasma Abeta42/Abeta40 ratio has potential as pre‐screener to identify Alzheimer's pathological changes in cognitively normal individuals with SCD.