Steps to Order the Elecsys® Alzheimer's Disease CSF Assays

Cerebrospinal fluid biomarkers support early diagnosis of Alzheimer’s Timely diagnosis of AD is an unmet need in clinical practice. The diagnosis of Alzheimer’s is often one of exclusion, determined by ruling out non-AD causes of symptoms through several evaluations such as cognitive exams, laboratory tests and neuroimaging. Unfortunately, this process not only could delay the formal diagnosis, but it was shown that clinical diagnosis can be inaccurate in approximately 23% of cases.2,3 The use of cerebrospinal fluid (CSF) biomarkers could positively impact clinical diagnosis for Alzheimer’s disease.

Roche’s FDA-cleared biomarkers represent all three main Alzheimer’s pathologies – amyloid plaques, tau tangles and neurodegeneration. With these biomarkers, identification of AD pathology in early disease stages (as early as mild cognitive impairment) when amyloid targeting therapies are most effective, is possible.1,2

 

 

The Elecsys AD CSF ratios have high concordance with β‑Amyloid positron emission tomography (PET) scan results.¹ The Elecsys assays combine both Abeta42 and tau proteins to give accurate and reliable results that can confirm amyloid pathology in early stages of the disease1,3 and aid in Alzheimer’s diagnosis. Compared to a PET scan imaging test in some geographies, these assays are more accessible and cost effective, meaning an accelerated and earlier path to a confirmed diagnosis is within reach for more people.

Ordering the Elecsys CSF biomarkers requires careful adherence to pre-analytical sample handling procedures, which are based on recommendations from the Alzheimer’s Association International guidelines1,4. The Abeta42 biomarker, is highly influenced by pre-analytical factors such as CSF collection and sample handling. Extra precautions for sample handling prior to testing are required to avoid Abeta42 loss. With this in mind, it’s important to contact your clinical laboratory partners to gather important ordering, collection, handling and transport instructions. Your lab will be able to provide you with the assay package insert and additional guidance, and in some cases also with the appropriate collection tubes.

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Steps to Order the Elecsys AD CSF Assays

  1. Discuss ordering process/workflow with your local clinical laboratory partner 
    • In-house vs sendout
    • Test code/EMR/diagnosis code/CPT code 
      • Reimbursement for Roche’s CSF test may be obtained using: 0445U (PLA code) to report the pTau181/AB42 ratio & 0459U for the tTau/AB42 ratio effective July 1, 2024. Prior to that, report 83520 x 2 (generic immunoassay CPT® code).
    • Request the test package insert and any additional guidance from your lab partner
  2. Establish operational pathway for conducting lumbar punctures/collecting CSF samples
    • Location
    • Performing personnel and/or other specialties (i.e. interventional radiology)
    • Patient education materials 
  3. Establish sample collection protocols. As amyloid-beta is “sticky,” collection in a low-bind (polypropylene) tube is recommended in the Alzheimer’s Association International Guidance and the Elecsys CSF assays package inserts.
    • Ensure availability of low-bind tube for CSF collection 
      • Tube type: 2.5 mL Low bind, False bottom tube (Sarstedt, 63.614.625). Polystyrene collection tubes are not acceptable as exposing of CSF to polystyrene tubes may decrease Abeta42 concentrations. 
      • Procedure and handling: The Alzheimer’s Association recommends a standardized protocol based on the drip collection method which reduces binding of Abeta42 to the syringe and instead allows for direct collecting into a low bind tube. 
    • Collect the sample following established protocol
  4. Transport the sample to clinical lab/clinical lab partner following instructions. Samples are stable:
    • At room temperature (5-25 C) for up to 5 days
    • Refrigerated (2-8 C) for up to 14 days
    • Frozen (-20 C) for up to 8 weeks with one freeze-thaw cycle
  5. Evaluate results based on the validated cut-off and within the clinical context Elecsys AD CSF results will either be:
    • Above cut-off = positive result, consistent with a positive amyloid PET scan result or
    • Below cut-off = negative result, consistent with a negative amyloid PET scan result

The Elecsys pre-analytical protocol allows for reduction of variability between sites and improvement in the accuracy of biomarker measurements and inter-lab comparison5

Adherence to the pre-analytical protocol supports the implementation of CSF assays in routine clinical use.

Step 1

Perform the lumbar puncture (LP) using gravity drip collection method.

Step 2

Do not use the first 2 mL of CSF for Elecsys AD Biomarker measurement.

Step 3

Subsequently collect at least 2.5 mL of CSF directly into the CSF tube (2.5 mL Low bind False bottom tube).

Step 4

Do not process the CSF sample before transport to the measuring site (eg, no mixing/inverting, no tube transfers, no aliquoting, no freezing, and normally no centrifugation) until measurement.

Step 5

Transport the samples to the measuring site (laboratory), where the sample is placed directly on the cobas e system for measurement.5

The CSF sample can be analyzed immediately after collection by directly placing the tube with false bottom CSF, 2.5 mL onto the analyzer. If storage and/or transport is necessary, samples can be transported/stored according to the graphic above. 

*Additional material required for CSF collection (but not available through Roche):

Product: 2.5 mL Low bind False bottom tube

Order Number: 63.614.625

Vendor: Sarstedt

References

  1. Elecsys Method Sheets: ms_08846634501; ms_08821909501; ms_08846715501; ms_08846693501; ms_08821941501.
  2. Cummings, J., Apostolova, L., Rabinovici, G.D. et al. Lecanemab: Appropriate Use Recommendations. J Prev Alzheimers Dis 10, 362–377 (2023).
  3. Hansson O. et al. Alzheimer's Dement. 2018; 14[11]:1470-1481.
  4. Hansson O, et al., Alzheimer’s Dement.2021;17:1575–1582.
  5. Hansson O, et al. Alzheimers Dement. 2020;12:e12137.