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The Power of Elecsys® in Alzheimer’s disease

Robust, clinically validated results to help ensure patients get the care they deserve

Alzheimer’s disease (AD) is a public health crisis.1 The total number of people with dementia is expected to grow to 152 million in 2050 globally.1 62 % of the cases are caused by AD.2  

More than 50% of patients with dementia have no formal diagnosis3-6 and, in recent surveys, half of carers have reported that an earlier diagnosis of AD would have been preferred.7

Biomarkers of amyloid and tau pathology support the diagnosis of Alzheimer's disease and facilitate clinical trial enrollment.8,9 Several studies have reinforced that certain imaging such as amyloid positron emission tomography (PET) and cerebrospinal fluid (CSF) biomarkers are valid proxies for neuropathological changes of AD.10

The Elecsys® AD CSF portfolio includes two assays11

Elecsys® β-Amyloid (1-42) CSF II
Elecsys® β-Amyloid (1-42) CSF II

 

Elecsys β-Amyloid (1-42) CSF II and Elecsys Phospho-Tau (181P) CSF are in vitro electrochemiluminescence immunoassays for the measurement of the β-Amyloid (1-42) (Abeta42) and Phospho-Tau (181P) (pTau181) protein concentrations in cerebrospinal fluid (CSF) from adult patients aged 55 years and older being evaluated for Alzheimer's disease (AD) and other causes of cognitive impairment to generate a pTau181/Abeta42 ratio value.

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Elecsys® Phospho-Tau (181P) CSF
Elecsys® Phospho-Tau (181P) CSF

 

Elecsys β-Amyloid (1-42) CSF II and Elecsys Phospho-Tau (181P) CSF are in vitro electrochemiluminescence immunoassays for the measurement of the β-Amyloid (1-42) (Abeta42) and Phospho-Tau (181P) (pTau181) protein concentrations in cerebrospinal fluid (CSF) from adult patients aged 55 years and older being evaluated for Alzheimer's disease (AD) and other causes of cognitive impairment to generate a pTau181/Abeta42 ratio value.

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Elecsys® AD CSF assays can detect amyloid positivity, enhancing diagnostic accuracy and physician confidence.12,13

 

Amyloid PET detects amyloid amyloid positivity in the brain, but has several limitations for clinical routine implementation: expensive technique, requires specialist units equipment, confers a radioactive burden to the patient.14-17

Elecsys® AD CSF assays are used to generate a pTau181/Abeta42 ratio value, which is 90% concordant to amyloid PET and provides an alternative solution for the detection of amyloid positivity.11,13

Distribution of pTau and Abeta42 CSF biomarkers

Distribution of pTau181 and Abeta42 CSF biomarkers colored by PET visual read classification11,13

Elecsys® pTau181/Abeta42 ratio achieves 90% concordance with amyloid PET. A result above the cutoff is consistent with a positive amyloid PET scan result.11,13

 

Concordance between CSF biomarker test results and amyloid PET visual read was assessed using 277 CSF samples from Biomarkers For Identifying Neurodegenerative Disorders Early and Reliably (BioFINDER) cohort of patients with subjective cognitive decline (SCD) and mild cognitive impairment (MCI)11,13

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Performance of CSF ratio cutoffs versus amyloid PET visual read11,13

Performance of CSF ratio cutoffs versus amyloid PET visual read11,13

  Cutoff (+)  
 Cutoff (-)    PPA %  NPA %  OPA %
Elecsys® pTau181/Abeta42 ratio  >0.023 ≤ 0.023 88.2 (84.4-91.2)

92.6 (89.1-95.1)

 90.2 (87.7-92.3)   
Note: PPA - Positive Percent Agreement; NPA - Negative Percent Agreement; OPA - Overall Percent Agreement. Values in parentheses are 95% confidence intervals calculated using a Wilson score method for binomial proportions.
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A clinically validated cutoff helps ensure an easier implementation of Elecsys® assays in your lab.13,19

 

Universal cutoff concentrations are already applied for many biomarkers in routine clinical use (e.g., HbA1c in diabetes mellitus).18 The next step is to apply the same standardization concept for AD biomarkers to help ensure universal interpretation of results.19

The Elecsys β-Amyloid (1-42) CSF II and Elecsys Phospho-Tau (181P) CSF assays are standardized against reference materials to ensure accuracy of results. The Elecsys pTau181/Abeta42 ratio cutoff is the result of clinical validation and assay standardization.11

The Elecsys pTau181/Abeta42 ratio cutoff for concordance with amyloid PET was established based on agreement with amyloid PET status by visual read.11,13

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Elecsys® AD CSF ratio cutoffs 11

Elecsys® AD CSF ratio cutoffs 11

      Cutoff (+)    Cutoff (-)   
 Elecsys pTau181/Abeta42 ratio   > 0.023   ≤ 0.023 

Your results are reliable with Elecsys® 11,20

 

Elecsys® AD CSF assays achieve highly accurate and precise results. This is supported by internal data11 and confirmed by the Alzheimer’s Association Quality Control rounds, where Elecsys® results outperform manual assays and automated assays.20

 

The performance of the test for African American, Asian, and other races had high uncertainty due to the limited number of patients studied.11

Testing of AD parameters becomes fast and fully integrated.11

 

Once the sample is placed on the analyzer, results are received within 18 minutes, a marked improvement compared to previous manual enzyme-linked immunoabsorbent assay (ELISA).11,19

Unlike most major vendors, that are limited to instrument size, with cobas® you can run the assays on a cobas e® immunoassay platform of your choice, from the smallest to the largest.11

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    References

    1. Alzheimers Disease International. (2018). World Alzheimer Report 2018. Available from: https://www.alz.co.uk/research/WorldAlzheimerReport2018.pdf. Accessed October 7, 2022.
    2. Knapp et al. (2014). Dementia UK: Update. © Alzheimer’s Society 2014
    3. Lopponen, M. et al. (2003). Diagnosing cognitive impairment and dementia in primary health care - a more active approach is needed. Age Ageing 32(6), 606-12.; 
    4. Boustani M, et al. (2003) Screening for Dementia in Primary Care: A Summary of the Evidence for the U.S. Preventive Services Task Force 2003;138(11):927–37; 
    5. Valcour VG, et al. (2000) The Detection of Dementia in the Primary Care Setting. Arch Intern Med. 2000;160(19):2964–8; 
    6. Lang L, et al.(2017) Prevalence and determinants of undetected dementia in the community: a systematic literature review and a meta-analysis. BMJ Open 
    7. Alzheimer Europe. European carers’ report (2018) Carer’s experiences of diagnosis in five European countries. 2018. Available at https://www.alzheimer-europe.org/resources/publications/2018-european-carers-report-carers-experiences-diagnosis-five-european. Accessed October 7, 2022.
    8. FDA (2018). Early AD: developing drugs for treatment, guidance for industry. Available at: https://www.fda.gov/downloads/Drugs/GuidanceComplianceRegulatoryInformation/Guidances/UCM596728.pdf. Accessed October 7, 2022.
    9. EMA (2018). Guidelines on the clinical investigation of medicines for the treatment of AD. Available at: https://www.ema.europa.eu/documents/scientific-guideline/guideline-clinical-investigation-medicines-treatment-Alzheimers-disease-revision-2_en.pdf. Accessed October 7, 2022.
    10.  Jack, CR, Jr., et al. (2018). "NIA-AA Research Framework: Toward a biological definition of Alzheimer's disease." Alzheimers Dement 14(4): 535-562.
    11. Elecsys® β‑Amyloid (1‑42) CSF II assay and Elecsys® Phospho‑Tau (181P) CSF assay method sheets.
    12. Rabinovici, G.D. et al. (2019). Association of Amyloid Positron Emission Tomography With Subsequent Change in Clinical Management Among Medicare Beneficiaries With Mild Cognitive Impairment or Dementia. JAMA 321(13), 1286-1294.
    13. Hansson, O. et al. (2018). CSF biomarkers of Alzheimer’s disease concord with amyloid-β PET and predict clinical progression: A study of fully automated immunoassays in BioFINDER and ADNI cohorts. Alzheimers Dement 14(11), 1470-1481
    14. Blennow, K, et al. (2015). "Amyloid biomarkers in Alzheimer's disease." Trends Pharmacol Sci 36(5): 297-309.
    15. Arnerić, SP, et al. (2017). "Cerebrospinal Fluid Biomarkers for Alzheimer's Disease: A View of the Regulatory Science Qualification Landscape from the Coalition Against Major Diseases CSF Biomarker Team." J Alzheimers Dis 55(1): 19-35.
    16. Frisoni, GB, et al. (2017). "Strategic roadmap for an early diagnosis of Alzheimer's disease based on biomarkers." Lancet Neurol 16(8): 661-676.
    17. Liu, JL, et al. (2017). Assessing the Preparedness of the U.S. Health Care System Infrastructure for an Alzheimer's Treatment, RAND Corporation.
    18. Use of Glycated Haemoglobin (HbA1c) in the Diagnosis of Diabetes Mellitus: Abbreviated Report of a WHO Consultation. Geneva: World Health Organization; 2011.
    19. Bittner, T, et al. (2016). "Technical performance of a novel, fully automated electrochemiluminescence immunoassay for the quantitation of beta-amyloid (1-42) in human cerebrospinal fluid." Alzheimers Dement 12(5): 517-526.
    20. Alzheimer's Association Quality Control: 2014 (Round 14) to 2020 (Round 34)