Cautions

A positive cerebrospinal fluid (CSF) beta-amyloid 42 (Abeta42), total Tau (t-Tau), or phosphorylated Tau (p-Tau181) result, or p-Tau181/Abeta42 ratio does not establish a diagnosis of Alzheimer disease (AD) or other cognitive disorder. These results should be interpreted in combination with other clinical diagnostic and radiologic evaluations.

An abnormal p-Tau181/Abeta42 ratio in the context of a normal Abeta42 may be observed in some individuals. In some situations, interindividual differences in overall concentration of Abeta peptide production and/or in p-Tau elevation stemming from other neurodegenerative disease may result in an abnormal p-Tau181/Abeta42 ratio.

To achieve the best clinical performance (ie, keep patient misclassification rate at a minimum), it is important that the recommended pre-analytical protocol for sample collection is followed. Based on the Alzheimer's Association international guidelines for consensus handling of CSF for clinical measurements of Abeta42 and Tau, CSF should be collected using the drip method and directly collected into a low bind polypropylene tube. The low bind polypropylene tube should be filled to at least 80% of the tube volume capacity. Failure to adhere to this sample collection recommendation may impact the measured Abeta42 concentration and may influence the interpretation relation to the laboratory used cut-offs.

Additionally, it is recognized that using the recommended Alzheimer's Association drip method may not be feasible for every patient collection scenario. If a different method for CSF collection is used, it is critical that the CSF is collected directly into a low bind polypropylene tube and sent to Mayo Clinic Laboratories per test recommendations.

Improper specimen handling or interindividual differences in overall concentration of Abeta peptide production may yield an abnormally low Abeta42 in the context of a normal p-Tau181/Abeta42 ratio. Results should be interpreted in concordance with other clinical information.

Exposure of CSF to polystyrene tubes can reduce concentrations of the amyloid Abeta42 by as much as 20% to 50% due to adherence of the sticky amyloid protein to polystyrene tube surface material, potentially altering clinical interpretation, including the p-Tau181/Abeta 42 ratio. p-Tau181 and t-Tau protein do not substantially adhere to polystyrene collection tubes.

Failure to adhere to the specimen collection instructions provided may result in falsely low Abeta42 concentrations and potential misdiagnosis of AD.

The performance of the test for African American, Asian, and other races has high uncertainty due to the limited number of patients studied.

There is no high-dose hook effect at Abeta42 concentrations up to 6000 pg/mL, p-Tau181 concentrations up to 300 pg/mL, and t-Tau concentrations up to 4267 pg/mL.

CSF biotin concentrations up to 1200 ng/mL do not interfere with this assay. Concentrations up to 1200 ng/mL may be present in specimens collected from patients taking extremely high doses of biotin up to 300 mg/day.(1) In a study among 54 healthy volunteers, supplementation with 20 mg/day biotin resulted in a maximum serum biotin concentration of 355 ng/mL one-hour postdose.(2)

In rare cases, some individuals can develop antibodies to mouse or other animal antibodies (often referred to as human anti-mouse antibodies [HAMA] or heterophile antibodies), which may cause interference in some immunoassays. The presence of antibodies to streptavidin or ruthenium can also rarely occur and may interfere in this assay. Caution should be used in interpretation of results, and the laboratory should be alerted if the result does not correlate with the clinical presentation.