Quest Diagnostic’s Beta-Amyloid 42/40 Ratio and Apolipoprotein E (APOE) Isoform Panel:

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Quest Diagnostic’s Beta-Amyloid 42/40 Ratio and Apolipoprotein E (APOE) Isoform Panel:

Several national reference and diagnostic laboratories including LabCorp, Quest Diagnostics, ARUP Labs, Mayo Laboratories, and Athena Diagnostics have commercially-available tests for specific biomarkers for the assessment of AD. Some of these test offerings measure a combination or panel of biomarkers. This course will highlight tests available from LabCorp, Quest Diagnostics and Athena Diagnostics.
Quest Diagnostic’s Beta-Amyloid 42/40 Ratio and Apolipoprotein E (APOE) Isoform Panel:
This panel measures the Amyloid Beta 42 (AB42) and Amyloid Beta 40 (AB40 )peptides derived from the proteolytic cleavage of beta-amyloid and the APOE isoforms as well as the total APOE in CSF. The test uses liquid chromatography/tandem mass spectrometry (LC/MS/MS) to measure and identify (1) the AB42 and AB40 peptides expressing the results as the AB42/40 ratio, and (2) the total APOE and the various APOE isoforms. It is only available for use on CSF specimens and is not for use on blood samples. The test panel is not FDA-approved and has been validated by Quest Diagnostics.
AB42/40 Ratio: In general, the presence of a higher level of the AB42 peptide biomarker and in turn a higher AB42/40 ratio, suggests a lower AD risk while a lower level of AB42 peptide biomarker or lower AB42/40 ratio suggests a higher risk of AD.
APOE Isoforms: The test panel measures the main isoforms of APOE which are the e2, e3 and e4 isoforms. Typically, the presence of mainly the e2 isoform of APOE suggests a lower risk of AD while the presence mainly of the e4 APOE isoform suggests a higher risk of AD. The presence mainly of the e3 isoform may suggest an average risk of AD.
The test panel employs an algorithm to assess the ratio of AB42 to AB40, the total APOE concentration, and the APOE isoforms to stratify patient risk for AD as low, average, or medium. A risk assessment score is calculated by the algorithm and compared to cutoff values that define the AD risk levels. Results are reported and interpreted as follows:
High Risk of AD:
  • Presence of the APOE e4 isoform peptide
  • An AB42/40 ratio <0.20
  • An algorithm calculated risk assessment score >1.419
Low risk of AD:
    • Presence of APOE e2 isoform peptide (in the absence of e4)
    • AB42/40 ratio >0.25
    • An algorithm calculated risk assessment score <-0.918
    Average risk of AD:
      • Presence of APOE e3 isoform peptide (in the absence of e4)
      • AB42/40 ratio of 0.20 to 0.25.
      • An algorithm calculated risk assessment score of 0.918 to 1.419
      The test panel is marketed to assess the likelihood of AD in adults with signs of mild cognitive impairment (MCI) or dementia. It is intended not as a general screen but to be used on adults exhibiting signs of MCI or dementia.
      It should be noted that the test panel has certain limitations. Although the results of the test may suggest the likelihood of AD as the underlying cause for dementia or MCI, the interpretation of the test results should be considered along with findings from medical and family history, physical, neurological and neuropsychological examination, and neuroimaging.