Effective April 29, 2024, Clinical Pathology Laboratories (CPL) is pleased to announce that Alzheimer’s Disease Evaluation, Cerebrospinal Fluid, will now be performed in-house by electrochemiluminescence immunoassay. Utilizing reagents and instrumentation manufactured by Roche Diagnostics, three biomarkers will be measured in patient CSF and then expressed as ratios.

According to studies performed by Roche Diagnostics, when expressed in ratios, these three biomarkers show a good concordance with amyloid pathology detection through positron emission tomography (PET) scanning.1,2 In addition, they are recommended for the purpose of AD diagnosis and clinical trial enrollment.3,4

β-Amyloid (1-42) Phospho-Tau (181P)/β-Amyloid (1-42)
Phospho-Tau (181P) Total-Tau/β-Amyloid (1-42)
Total-Tau
Biomarkers Measured Ratios Reported
Phospho-Tau (181P)/β-Amyloid (1-42) 90.2 % (87.7% - 92.3%)
Total-Tau/β-Amyloid (1-42) 89.2% (86.5% - 91.3%)
Ratios Overall Percent Agreement with PET

β-Amyloid (1-42) has the propensity to form aggregates and oligomers which form fibrils that accumulate into β-Amyloid plaques and is a high-specificity marker of amyloid pathology. Phospho-Tau (181P) can reflect the formation of hyperphosphorylated tau at position 181 and represents their accumulation in neurofibrillary tangles. Total-Tau is a marker of neurodegeneration, which mirrors the intensity of neuronal damage, and is a high-specificity marker of neurofibrillary tangles.

Results for the three individual biomarkers are not intended to be used as stand-alone tests. They should only be used to calculate the appropriate ratios.

Phospho-Tau (181P)/β-Amyloid (1-42)

≤ 0.0230 - A negative result consistent with a negative amyloid PET scan result.

> 0.0230 - A positive result consistent with a positive amyloid PET scan result.
Total-Tau/β-Amyloid (1-42)

≤ 0.280 - A negative result consistent with a negative amyloid PET scan result.

> 0.280 - A positive result consistent with a positive amyloid PET scan result.
Interpretation of Biomarker Ratio Results

Please note: A positive Phospho-Tau (181P)/β-Amyloid (1-42) or Total-Tau/β-Amyloid (1-42) ratio result in CSF does not establish a diagnosis of Alzheimer’s disease and should always be interpreted in conjunction with clinical information.

Specimen Collection and Transportation

Due to the sticky properties of the β-Amyloid (1-42) peptide to the test tube, specimens should only be collected in the recommended tubes strictly following manufacture collection and transport instructions.

Most impactful on the β-Amyloid (1-42) concentrations are:

  1. Tube type - collect into polypropylene tubes (low binding). CSF exposed to polystyrene tubes leads to 20-50%reduction in β-Amyloid (1-42) concentration due to adherence.
    1. Tube Required for CSF collection:
      1. Product - 2.5 mL low binding false-bottom tube
      2. Order Number - 63.614.625
      3. Vendor - Sarstedt
  2. Tube filling volume - fill the tube to the mark (at least 2.5 mL).
  3. Transfer of CSF from one tube to another should be limited.
  4. Transportation conditions – the preferred specimen transport temperature is frozen.
  5. Mixing/inverting - it is not recommended for fresh samples as it can affect β-Amyloid (1-42) concentrations.

Please contact your Account Executive to receive collection kits that include the Sarstedt 2.5 mL low binding false-bottom tube.

Please see link* below for more collection and transport information.

The Roche Elecsys® Alzheimer’s CSF Assays: https://usinfo.roche.com/Alzheimers-HCP-Download-Page.html

* Please note that this link is hosted by Roche Diagnostics, and CPL does not have editorial control over linked content.

References:

  1. Elecsys Method Sheet: ms_08821941190, ms_08846693160, ms_08846685190
  2. Hansson O, et al. Alzheimers Dement. 2018;14(11):1470-1481.
  3. FDA. Early AD: developing drugs for treatment, guidance for industry. 2018. https://www.fda.gov/downloads/Drugs/GuidanceComplianceRegulatoryInformation/Guidances/UCM596728.pdf (accessed October 26, 2022).
  4. EMA. Guidelines on the clinical investigation of medicines for the treatment of AD. 2018. https://www.ema.europa.eu/documents/scientific-guideline/guideline-clinical-investigation-medicines-treatment-Alz-heimers-disease-revision-2_en.pdf (accessed October 26, 2022).