Clinical performance and robustness evaluation of plasma amyloid-beta(42/40) prescreening

• Introduction Further evidence is needed to support the use of plasma amyloid beta (A beta) biomarkers as Alzheimer's disease prescreening tools. This study evaluated the clinical performance and robustness of plasma A beta(42)/A beta(40) for amyloid positivity prescreening. Methods Data were collected from 333 BioFINDER and 121 Alzheimer's Disease Neuroimaging Initiative study participants. Risk and predictive values versus percentile of plasma A beta(42)/A beta(40) evaluated the actionability of plasma A beta(42)/A beta(40), and simulations modeled the impact of potential uncertainties and biases. Amyloid PET was the brain amyloidosis reference standard. Results Elecsys plasma A beta(42)/A beta(40) could potentially rule out amyloid pathology in populations with low-to-moderate amyloid positivity prevalence. However, simulations showed small measurement or pre-analytical errors in A beta(42) and/or A beta(40) cause misclassifications, impacting sensitivity or specificity. The minor fold change between amyloid PET positive and negative cases explains the biomarkers low robustness. Discussion Implementing plasma A beta(42)/A beta(40) for routine clinical use may pose significant challenges, with misclassification risks. Highlights Plasma A beta(42)/A beta(40) ruled out amyloid PET positivity in a setting of low amyloid-positive prevalence. Including (pre-) analytical errors or measurement biases caused misclassifications. Plasma A beta(42)/A beta(40) had a low inherent dynamic range, independent of analytical method. Other blood biomarkers may be easier to implement as robust prescreening tools.

Subject headings

MEDICIN OCH HÄLSOVETENSKAP  -- Medicinska och farmaceutiska grundvetenskaper -- Neurovetenskaper (hsv//swe)

MEDICAL AND HEALTH SCIENCES  -- Basic Medicine -- Neurosciences (hsv//eng)

Keyword

Alzheimer's disease

amyloid

biomarkers

blood biomarkers

prescreening

biomarkers

Neurosciences & Neurology

Publication and Content Type

ref (subject category)

art (subject category)