Test Catalog

Test Id : ADBIO

Biogen Program, Alzheimer Disease Evaluation, Spinal Fluid

Useful For
Suggests clinical disorders or settings where the test may be helpful

Assessment of adults with cognitive impairment being evaluated for Alzheimer disease and other causes of cognitive impairment

 

Biogen’s Amyloid Beta Confirmed Program

 

This test should not be used to predict the development of dementia or other neurologic conditions or to monitor response to therapies.

Highlights

Measurement of beta-amyloid (1-42)(Abeta42), total-Tau, and phosphorylated-Tau (p-Tau) in cerebrospinal fluid (CSF) is useful in the differential diagnosis of Alzheimer disease (AD) and other causes of cognitive impairment.

 

These assays are being proposed as an alternative/adjunct to imaging studies to assess AD pathology.

 

The p-Tau/Abeta42 ratio provides excellent concordance with amyloid positron emission tomography (PET) scan to assess the presence of amyloid deposition in patients with AD.

Method Name
A short description of the method used to perform the test

Electrochemiluminescent Immunoassay (ECLIA)

NY State Available
Indicates the status of NY State approval and if the test is orderable for NY State clients.

Yes

Reporting Name
Lists a shorter or abbreviated version of the Published Name for a test

Biogen Alzheimers Disease Eval, CSF

Aliases
Lists additional common names for a test, as an aid in searching

ABeta

Amyloid Beta 42

Beta-Amyloid 42

Phosphorylated Tau

pTau

Total Tau

tTau

Specimen Type
Describes the specimen type validated for testing

CSF

Ordering Guidance

This test is only available as part of Biogen's Amyloid Beta Confirmed Program. For more information on program enrollment, visit https://news.mayocliniclabs.com/amyloid-beta-confirm/.

 

Specimens for this program are accepted from the United States (inclusive of US and Puerto Rico). Test requests for this sponsored test may only be submitted by US-based healthcare providers.

 

To request testing outside of the sponsored program, order ADEVL / Alzheimer Disease Evaluation, Spinal Fluid.

Necessary Information

The following information is required.

-Current disease state (mild, moderate, or severe)

-Zip code of patient

-Sponsor registration code

Note: Not applicable (NA) is not an acceptable response.

Specimen Required
Defines the optimal specimen required to perform the test and the preferred volume to complete testing

Patient Preparation: For 12 hours before specimen collection do not take multivitamins or dietary supplements containing biotin (vitamin B7), which is commonly found in hair, skin, and nail supplements and multivitamins.

Supplies: Alzheimer's Disease Evaluation (ADEVL) Collection Kit (T836)

Collection Container/Tube:

Preferred: CSF AD Biomarker Tube (2.5 mL)

Acceptable: Sarstedt 72.703.600 (1.5 mL) or Sarstedt 72.694.600 (2 mL)

Specimen Volume: 1.5-2 mL

Collection Instructions:

1. Perform lumbar puncture and discard the first 1 to 2 mL of cerebrospinal fluid (CSF).

2. Collect CSF directly into one of the listed collection tubes until the tube is at least 50% full.*

Note: Polystyrene collection tubes are not acceptable. Exposure of CSF to polystyrene tubes may result in falsely low Abeta42 concentrations. For more information see Cautions.

*The Alzheimer's Association consensus protocol for handling of CSF for clinical measurements of Abeta42 and tau recommends using the drip method for CSF collection and directly collecting into a low bind polypropylene tube. Although some clinicians prefer the syringe pull method due to speed of collection, the drip method reduces the risk of Abeta42 binding to the plastic of any syringe used.

Forms

Specimen Minimum Volume
Defines the amount of sample necessary to provide a clinically relevant result as determined by the Testing Laboratory

See Specimen Required

Reject Due To
Identifies specimen types and conditions that may cause the specimen to be rejected

Gross hemolysis Reject
Gross lipemia OK
Gross icterus Reject

Specimen Stability Information
Provides a description of the temperatures required to transport a specimen to the performing laboratory, alternate acceptable temperatures are also included

Specimen Type Temperature Time Special Container
CSF Refrigerated (preferred) 14 days BlueTop SARSTEDT
Frozen 30 days BlueTop SARSTEDT
Ambient 12 hours BlueTop SARSTEDT

Useful For
Suggests clinical disorders or settings where the test may be helpful

Assessment of adults with cognitive impairment being evaluated for Alzheimer disease and other causes of cognitive impairment

 

Biogen’s Amyloid Beta Confirmed Program

 

This test should not be used to predict the development of dementia or other neurologic conditions or to monitor response to therapies.

Clinical Information
Discusses physiology, pathophysiology, and general clinical aspects, as they relate to a laboratory test

Currently the diagnosis of probable Alzheimer disease (AD) is made based on clinical symptoms, largely by the exclusion of other causes of dementia, with postmortem evidence of AD pathology required to confirm the diagnosis. Two common neuropathologic features found in the brain of patients with AD dementia are the presence of plaques composed of beta-amyloid (Abeta) peptides and intracellular neurofibrillary tangles containing hyperphosphorylated Tau (tubulin-associated unit) proteins. These 2 groups of molecules are the most established biomarkers of the disease used in clinical and research practice. Positron emission tomography (PET) imaging using US Food and Drug Administration approved amyloid radiotracer to visualize the presence of amyloid lesions in the cerebral cortex is available in some specialized centers. Measuring Abeta peptides and Tau proteins in cerebrospinal fluid (CSF) is being proposed as an alternative/adjunct to imaging studies to assess AD pathology. Recently the use of these biomarkers has been included in the new consensus research diagnostic criteria for AD, mild cognitive impairment (MCI), and preclinical AD, proposed by the National Institute on Aging and Alzheimer's Association (NIA-AA) Research Framework.

 

The CSF assays included in this evaluation are beta-amyloid (1-42; Abeta42), total-Tau (t-Tau) and phosphorylated-Tau (p-Tau).

 

Abeta42 is approximately 4 kDa protein of 42 amino acids that is formed following proteolytic cleavage of a transmembrane protein known as amyloid precursor protein (APP). Due to its hydrophobic nature, Abeta42 has the propensity to form aggregates and oligomers. Oligomers form fibrils that accumulate into amyloid plaques. These pathological changes in Abeta42 are reflected by the decrease in the CSF concentrations of Abeta42 and/or by the increase in the brain uptake of specific tracers during beta-amyloid PET.

 

Tau is present as 6 isoforms in human brain tissue. These isoforms are generated by alternative splicing of the pre-mRNA. The t-Tau assay measures all these isoforms. The most common post-translational modification of Tau proteins is phosphorylation. During neurodegeneration, abnormal phosphorylation leads to the formation of intracellular neurofibrillary tangles composed of the Tau protein that has undergone hyperphosphorylation and developed aggregates of hyper-phosphorylated Tau proteins called p-Tau. The p-Tau assay detects p-Tau at threonine 181 (p-Tau 181).

 

Pathological changes associated with AD are reflected by an increase in the CSF concentrations of t-Tau and p-Tau. Increases in CSF t-Tau reflect the intensity of the neuronal and axonal damage and degeneration and is associated with a faster progression from MCI to AD. Increases in CSF p-Tau concentrations are also associated with a faster progression from MCI to AD with more rapid cognitive decline in AD patients and in mild AD dementia cases.

 

The Alzheimer's Association has developed an appropriate use criterion (AUC) in order to guide safe and optimal use of CSF testing for AD pathology detection in the diagnostic process. The use of CSF biomarker testing may be indicated for the following patient groups:

1) Patients with subjective cognitive decline (SCD) who are considered to be at increased risk for AD

2) Patients with MCI that is persistent, progressing, and unexplained

3) Patients with symptoms that suggest possible AD

4) MCI or dementia with an onset at an early age (less than 65)

5) Patients meeting core clinical criteria for probable AD with typical age of onset

6) Patients whose dominant symptom is a change in behavior (eg, Capgras syndrome, paranoid delusions, unexplained delirium, combative symptoms, and depression) and where AD diagnosis is being considered.

 

Ultimately, the decision to initiate CSF testing for the evaluation of suspected AD is also based on the clinical judgment of expert providers and the patient's individual presentation.

Reference Values
Describes reference intervals and additional information for interpretation of test results. May include intervals based on age and sex when appropriate. Intervals are Mayo-derived, unless otherwise designated. If an interpretive report is provided, the reference value field will state this.

Beta-amyloid (1-42) (Abeta42): >1026 pg/mL

Total-Tau: < or =238 pg/mL

Phosphorylated-Tau (p-Tau) 181: < or =21.7 pg/mL

p-Tau/Abeta42: < or =0.023

Interpretation
Provides information to assist in interpretation of the test results

A beta-amyloid (1-42; Abeta42) result greater than 1026 pg/mL is consistent with a negative amyloid positron emission tomography (PET) scan. A negative amyloid PET scan indicates the presence of no or sparse neuritic plaques and is inconsistent with a neuropathological diagnosis of Alzheimer disease (AD). An Abeta42 result greater than 1026 pg/mL is associated with a reduced likelihood that a patient's cognitive impairment is due to AD. Total Tau (t-Tau) and phosphorylated Tau (p-Tau) cerebrospinal fluid (CSF) concentrations increase approximately 2 to 3-times as much in patients with mild-moderate AD as compared to age-matched controls. A t-Tau and/or p-Tau concentration of less than or equal to 238 pg/mL and less than or equal to 21.7 pg/mL, respectively, reduces the likelihood that a patient's cognitive impairment is due to AD.

 

The use of p-Tau/Abeta42 ratio provides better concordance with amyloid PET scan when compared to Abeta42, p-Tau and t-Tau individually. A cut-off of 0.023 provides optimal balance between NPA (negative % agreement) and PPA (positive % agreement) when compared to amyloid PET results. A p-Tau/Abeta42 ratio of less than or equal to 0.023 has a 92% NPA with normal amyloid PET. A ratio of greater than 0.023 has a 92% PPA with abnormal amyloid PET.

 

High CSF t-Tau protein concentrations are found in other neurodegenerative diseases such as prion disease or Creutzfeldt-Jakob disease (CJD). In this situation, an elevated t-Tau concentration and an increased t-Tau to p-Tau ratio has a very high specificity for differential diagnoses of CJD.

 

Abnormal (+)/Normal (-)

Individual comments for AD reporting values

Abeta42 (-)

Phosphorylated-Tau (-)

Total-Tau (-)

Normal concentrations of Abeta42, phosphorylated-Tau (p-Tau), and total-Tau (t-Tau) concentrations are present in CSF. These results are not consistent with the presence of pathological changes associated with Alzheimer's disease.

Abeta42 (+)

p-Tau (-)

t-Tau (-)

Abnormal Abeta42 concentrations are present in CSF.

P-Tau and t-Tau concentrations are normal.

These results may be consistent with Alzheimer's related pathologic change. 

Abeta42 (+)

p-Tau (+)

t-Tau (-)

Abnormal Abeta42 and p-Tau concentrations are present in CSF.

The t-Tau concentration is normal.

These results are consistent with the presence of Alzheimer's disease.

Abeta42 (+)

p-Tau (+)

t-Tau (+)

Abnormal Abeta42, p-Tau and t-Tau concentrations are present in CSF. These results are consistent with the presence of Alzheimer's disease.

Abeta42 (+)

p-Tau (-)

t-Tau (+)

Abnormal Abeta42 and t-Tau concentrations are present in CSF.

The p-Tau concentration is normal.

These results may be consistent with Alzheimer's related pathologic change.

Abeta42 (-)

p-Tau (+)

t-Tau (-)

Abnormal p-Tau concentrations are present in CSF.

Abeta42 and t-Tau concentrations are normal.

These results are not consistent with the presence of pathological changes associated with Alzheimer's disease. 

Abeta42 (-)

p-Tau (-)

t-Tau (+)

Abnormal t-Tau concentrations are present in CSF.

The Abeta42 and p-Tau concentrations are normal.

These results are not consistent with the presence of pathological changes associated with Alzheimer's disease.

Abeta42 (-)

p-Tau (+)

t-Tau (+)

Abnormal p-Tau and t-Tau concentrations are present in CSF.

The Abeta42 concentration is normal.

These results are not consistent with the presence of pathological changes associated with Alzheimer's disease. 

 

This table and interpretations are based on the NIA-AA Research Framework diagnostic recommendations.(1)

Cautions
Discusses conditions that may cause diagnostic confusion, including improper specimen collection and handling, inappropriate test selection, and interfering substances

A positive cerebrospinal fluid (CSF) beta-amyloid 42 (Abeta42), total Tau (t-Tau), or phosphorylated Tau (p-Tau) result, or p-Tau/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-Tau/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-Tau/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 to 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 as 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-Tau/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-Tau/Abeta 42 ratio. p-Tau 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.

Clinical Reference
Recommendations for in-depth reading of a clinical nature

1. Jack CR Jr, Bennett DA, Blennow K, et al: NIA-AA Research Framework: Toward a biological definition of Alzheimer's disease. Alzheimers Dement. 2018 Apr;14(4):535-562

2. Lifke V, Kollmorgen G, Manuilova E, et al: Elecsys total-Tau and phospho-Tau (181P) CSF assays: Analytical performance of the novel, fully automated immunoassays for quantification of tau proteins in human cerebrospinal fluid. Clin Biochem. 2019 Oct;72:30-38

3. Willemse EAJ, van Maurik IS, Tijms BM, et al: Diagnostic performance of Elecsys immunoassays for cerebrospinal fluid Alzheimer's disease biomarkers in a nonacademic, multicenter memory clinic cohort: The ABIDE project. Alzheimers Dement (Amst). 2018 Sep 12;10:563-572

4. Hansson O, Seibyl J, Stomrud E, et al: CSF biomarkers of Alzheimer's disease concord with amyloid-beta PET and predict clinical progression: A study of fully automated immunoassays in BioFINDER and ADNI cohorts. Alzheimers Dement. 2018 Nov;14(11):1470-1481

5. Schindler SE, Gray JD, Gordon BA, et al: Cerebrospinal fluid biomarkers measured by Elecsys assays compared to amyloid imaging. Alzheimers Dement. 2018 Nov;14(11):1460-1469

6. Shaw LM, Arias J, Blennow K, et al: Appropriate use criteria for lumbar puncture and cerebrospinal fluid testing in the diagnosis of Alzheimer's disease. Alzheimers Dement. 2018; 14(11):1505-1521

7. Hansson O, Batrla R, Brix B, et al: The Alzheimer's Association international guidelines for handling of cerebrospinal fluid for routine clinical measurements of amyloid beta and tau. Alzheimers Dement. 2021 Sep;17(9):1575-1582. doi: 10.1002/alz.12316

Method Description
Describes how the test is performed and provides a method-specific reference

Beta-amyloid (1-42):

The Roche cobas assay for determining beta-amyloid (1-42) in cerebrospinal fluid (CSF) uses a sandwich assay principle. A biotinylated monoclonal beta-amyloid (1-42) antibody (21F12) and a monoclonal beta-amyloid (1-42) specific antibody (3D6) labeled with a ruthenium complex react to form a sandwich complex. Streptavidin-coated microparticles are added, and the interaction between biotin and streptavidin allows the complex to become bound to the solid phase. The reaction mixture is then aspirated into the measuring cell, microparticles are captured onto the electrode, and the application of voltage induces chemiluminescent emission, which is measured by a photomultiplier.(Package insert: Elecsys beta-amyloid (1-42) CSF. Roche Diagnostics; 09/2019)

 

Total-Tau:

The Roche cobas assay for determining total-Tau in CSF uses a sandwich assay principle. Two biotinylated monoclonal Tau-specific antibodies (5.28.464 and 4.35.411) and a monoclonal Tau-specific antibody (PC1C6) labeled with a ruthenium complex react to form a sandwich complex. Streptavidin-coated microparticles are added, and the interaction between biotin and streptavidin allows the complex to become bound to the solid phase. The reaction mixture is then aspirated into the measuring cell, microparticles are captured onto the electrode, and the application of voltage induces chemiluminescent emission, which is measured by a photomultiplier.(Package insert: Elecsys Total-Tau CSF. Roche Diagnostics; 10/2019)

 

Phosphorylated-Tau:

The Roche cobas assay for determining phosphorylated-Tau in CSF uses a sandwich assay principle. A biotinylated monoclonal antibody specific for phosphorylation at threonine 181 (11H5V1) and a monoclonal Tau-specific antibody (PC1C6) labeled with a ruthenium complex react to form a sandwich complex. Streptavidin-coated microparticles are added, and the interaction between biotin and streptavidin allows the complex to become bound to the solid phase. The reaction mixture is then aspirated into the measuring cell, microparticles are captured onto the electrode, and the application of voltage induces chemiluminescent emission, which is measured by a photomultiplier.(Package insert: Elecsys pTau (181P) CSF. Roche Diagnostics; 08/2019)

PDF Report
Indicates whether the report includes an additional document with charts, images or other enriched information

No

Day(s) Performed
Outlines the days the test is performed. This field reflects the day that the sample must be in the testing laboratory to begin the testing process and includes any specimen preparation and processing time before the test is performed. Some tests are listed as continuously performed, which means that assays are performed multiple times during the day.

Tuesday, Wednesday, Thursday

Report Available
The interval of time (receipt of sample at Mayo Clinic Laboratories to results available) taking into account standard setup days and weekends. The first day is the time that it typically takes for a result to be available. The last day is the time it might take, accounting for any necessary repeated testing.

1 to 8 days

Specimen Retention Time
Outlines the length of time after testing that a specimen is kept in the laboratory before it is discarded

12 months

Performing Laboratory Location
Indicates the location of the laboratory that performs the test

Rochester

Fees
Several factors determine the fee charged to perform a test. Contact your U.S. or International Regional Manager for information about establishing a fee schedule or to learn more about resources to optimize test selection.

  • Authorized users can sign in to Test Prices for detailed fee information.
  • Clients without access to Test Prices can contact Customer Service 24 hours a day, seven days a week.
  • Prospective clients should contact their Regional Manager. For assistance, contact Customer Service.

Test Classification
Provides information regarding the medical device classification for laboratory test kits and reagents. Tests may be classified as cleared or approved by the US Food and Drug Administration (FDA) and used per manufacturer instructions, or as products that do not undergo full FDA review and approval, and are then labeled as an Analyte Specific Reagent (ASR) product.

This test was developed, and its performance characteristics determined by Mayo Clinic in a manner consistent with CLIA requirements. This test has not been cleared or approved by the US Food and Drug Administration.

CPT Code Information
Provides guidance in determining the appropriate Current Procedural Terminology (CPT) code(s) information for each test or profile. The listed CPT codes reflect Mayo Clinic Laboratories interpretation of CPT coding requirements. It is the responsibility of each laboratory to determine correct CPT codes to use for billing.

CPT codes are provided by the performing laboratory.

83520 x 3

Test Setup Resources

Setup Files
Test setup information contains test file definition details to support order and result interfacing between Mayo Clinic Laboratories and your Laboratory Information System.

Excel | Pdf

Sample Reports
Normal and Abnormal sample reports are provided as references for report appearance.

Normal Reports | Abnormal Reports

SI Sample Reports
International System (SI) of Unit reports are provided for a limited number of tests. These reports are intended for international account use and are only available through MayoLINK accounts that have been defined to receive them.

SI Normal Reports | SI Abnormal Reports