Test Catalog

Test Id : AMYR

Beta-Amyloid Ratio (1-42/1-40), Spinal Fluid

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

Assisting in the evaluation of adult patients, aged 55 years and older, presenting with cognitive impairment and who are being assessed for Alzheimer disease and other causes of cognitive decline

 

This test is not intended as a screening or stand-alone diagnostic assay.

Highlights

This test measures the beta-amyloid ratio (1-42/1-40) in cerebrospinal fluid. The beta-amyloid ratio (1-42/1-40) is a surrogate marker of amyloid plaque burden, caused by increased deposition of beta-amyloid 1-42 in the brain.

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

Chemiluminescent Immunoassay

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

Beta-Amyloid Ratio (1-42/1-40), CSF

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

Amyloid Beta 42

Beta-Amyloid 42

Amyloid Beta 40

Beta-Amyloid 40

Amyloid ratio

Ab42/Ab40 ratio

Specimen Type
Describes the specimen type validated for testing

CSF

Ordering Guidance

This test is intended for use in adult patients, aged 55 years and older. If evaluating an individual 54 years or younger, order ADEVL / Alzheimer's Disease Evaluation, Spinal Fluid.

 

This test only measures the beta-amyloid ratio (1-42/1-40) in cerebrospinal spinal fluid (CSF). Individual beta-amyloid 1-42 and 1-40 concentrations are not reported. If measurement of additional neurodegeneration markers such as total Tau, phosphorylated Tau (p-Tau181), beta-amyloid (1-42), and the p-Tau/beta-amyloid 42 ratio are desired, order ADEVL / Alzheimer's Disease Evaluation, Spinal Fluid.

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

Collection Container/Tube:

Preferred: Sarstedt 1.5 mL tube (Ref. 72.703.600), Collect at least 750 mcL of CSF or (> or =50% full).

Acceptable: Sarstedt 10 mL tube Ref. 62.610.018, Collect at least 5 mL of CSF (> or =50% full).

All tubes should be filled to between 50% to 100% of the total empty container volume. Specimens received with less than the required fill volume may be rejected.

Submission Container/Tube:

Specimen Volume: 0.75 to1.5 mL or at least 50% container volume

Collection Instructions:

1. This test is intended for use in adult patients, aged 55 years and older. Do not collect cerebrospinal fluid (CSF) for this test if the patient is younger than 55 years of age.

2. Perform lumbar puncture and discard the first 1 to 2 mL of CSF. Note: CSF collection should be performed by the gravity drip method.

3. Discard any visibly blood contaminated CSF.

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

5. If transporting frozen, freeze sample upright prior to placing in transport container.

6. If transporting refrigerate, tubes should be transported upright.

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

Forms

If not ordering electronically, complete, print, and send a Neurology Specialty Testing Client Test Request (T732) with the specimen. 

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 Reject
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 Frozen (preferred) 90 days
Refrigerated 14 days
Ambient 48 hours

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

Assisting in the evaluation of adult patients, aged 55 years and older, presenting with cognitive impairment and who are being assessed for Alzheimer disease and other causes of cognitive decline

 

This test is not intended as a screening or stand-alone diagnostic assay.

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

One of the neuropathologic features found in the brain of patients with Alzheimer disease (AD) is the presence of plaques composed of beta-amyloid. The two beta-amyloid peptides evaluated on this assay are 1-40 and 1-42. Beta-amyloid 1-40 typically exists at a higher physiological concentration than beta-amyloid 1-42. In AD, beta-amyloid 1-42 accumulation, either by overproduction or decreased clearance, leads to aggregation into plaques and neurotoxicity. Beta-amyloid 1-40 is much less prone to aggregation, with levels remaining unchanged when comparing patients with AD to healthy individuals.

 

In cerebrospinal fluid (CSF), approximately a 50% reduction in beta-amyloid 1-42 concentrations has been observed in AD patients compared to the concentrations found in cognitively normal individuals. This is believed to be as consequence of the decrease in soluble beta-amyloid 1-42 in the brain interstitial fluid as the peptide becomes increasingly insoluble and form deposits in the form of large numbers of diffuse and neuritic plaques. Unlike beta-amyloid 1-42, the values for beta-amyloid 1-40 in CSF remain relatively stable in individuals regardless of the presence of amyloid-pathology.

 

Various studies have demonstrated that the use of the beta-amyloid ratio (1-42/1-40) ratio increase diagnostic accuracy for AD versus use of beta-amyloid 1-42 alone. Beta-amyloid ratio (1-42/1-40) demonstrates high concordance with amyloid positron emission tomography (PET) when distinguishing amyloid deposition due to AD from alternative causes of mild cognitive impairment or dementia. In addition, the use of the CSF beta-amyloid ratio (1-42/1-40) could partially mitigate the effect of some preanalytical confounders that have been described to alter the results of beta-amyloid 1-42 in CSF.

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 Ratio (1-42/1-40): > or =0.073

Interpretation
Provides information to assist in interpretation of the test results

A normal beta-amyloid ratio (1-42/1-40) of 0.073 and above is consistent with a negative (normal) amyloid positron emission tomography (PET) scan result. This result indicates a reduced likelihood that a patient’s cognitive impairment is due to Alzheimer disease (AD).

 

A beta-amyloid ratio (1-42/1-40) between 0.059 and 0.072 (likely positive) is more likely consistent with a positive amyloid PET scan result. A likely positive result does not establish a diagnosis of AD or other cognitive disorders and has increased uncertainty in regard to amyloid PET positivity.

 

An abnormal beta-amyloid ratio (1-42/1-40) of 0.058 and below is consistent with a positive (abnormal) amyloid PET scan result. This result does not establish a diagnosis of AD or other cognitive disorder.

 

The performance of the beta-amyloid ratio (1-42/1-40) compared to amyloid PET is shown below and described as amyloid PET-positive predictive value (indicated as Predictive Value: PV):

 

 

Beta-Amyloid Ratio

(1-42/1-40)

Amyloid PET

 

 

Positive

Negative

Total

Amyloid PET-positive PV, %

95% CI, %

Positive (abnormal)

(ratio < or =0.058)

 

171

 

6

 

177

 

96.6

 

92.8-98.4

Likely positive

(ratio 0.059 to  0.072)

 

13

 

9

 

22

 

59.1

 

38.7-66.7

Negative

(ratio > or =0.073)

 

15

 

78

 

93

 

16.1

 

10.0-24.9

 

Total number of patients

 

199

 

93

 

293

 

 

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

The beta-amyloid ratio (1-42/1-40) results must be interpreted in conjunction with other diagnostic tools such as neurological examination, neurobehavioral tests, imaging, and routine laboratory tests.

 

The safety and effectiveness of this test have not been established for predicting development of dementia or other neurologic conditions or for monitoring the effect of any therapeutic product.

 

The amyloid ratio (1-42/1-40) has not been shown to correlate with disease severity.

 

Results obtained with different assay methods or kits may be different and cannot be used interchangeably.

 

In rare cases, some individuals can develop antibodies to mouse or other animal antibodies (often referred to as human anti-mouse antibodies (HAMA) or heterophile antibodies, which may cause interference in some immunoassays. Caution should be used in interpretation of results and the laboratory should be alerted if the result does not correlate with the clinical presentation.

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

1. Wiltfang J, Esselmann H, Bibl M, et al: Amyloid beta peptide ratio 42/40 but not A beta 42 correlates with phospho-Tau in patients with low- and high-CSF A beta 40 load. J Neurochem. 2007 May;101(4):1053-1059. doi: 10.1111/j.1471-4159.2006.04404.x

2. Dumurgier J, Schraen S, Gabelle A, et al: Cerebrospinal fluid amyloid-beta 42/40 ratio in clinical setting of memory centers: a multicentric study. Alzheimers Res Ther. 2015 Jun 1;7(1):30. doi: 10.1186/s13195-015-0114-5

3. Gervaise-Henry C, Watfa G, Albuisson E, et al: Cerebrospinal fluid ABeta42/ABeta40 as a means to limiting tube- and storage-dependent pre-analytical variability in clinical setting. J Alzheimers Dis. 2017;57(2): 437-445. doi: 10.3233/JAD-160865

4. Toombs J, Foiani MS, Wellington H, et al: Amyloid Beta peptides are differentially vulnerable to preanalytical surface exposure, an effect incompletely mitigated by the use of ratios. Alzheimers Dement (Amst). 2018 Mar 22;10:311-321. doi: 10.1016/j.dadm.2018.02.005

5. Delaby C, Munoz L, Torres S, et al: Impact of CSF storage volume on the analysis of Alzheimer's disease biomarkers on an automated platform. Clin Chim Acta. 2019 Mar;490:98-101. doi: 10.1016/j.cca.2018.12.021

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

beta-Amyloid 1-40:

The Lumipulse G beta-Amyloid 1-40 is an assay system for the quantitative measurement of beta-amyloid 1-40 in cerebrospinal fluid (CSF) specimens based on chemiluminescent enzyme immunoassay (CLEIA) technology by a specific two-step sandwich immunoassay method on the Lumipulse G System. The specimen is added to the particle solution. The beta-amyloid 1-40 in the specimen specifically binds to anti-beta-amyloid 1-40 monoclonal mouse antibody on the particles and antigen-antibody immunocomplexes are formed. The particles are then washed and rinsed to remove unbound materials. Alkaline phosphatase labeled anti-beta-amyloid monoclonal antibody is added that specifically binds to the prior formed immunocomplexes on the particles and additional immunocomplexes are formed. The particles are washed and rinsed to remove unbound materials. Substrate solution is added and mixed with the particles. 3-(2'-spiroadamantane)-4-methoxy-4-(3"-phosphoryloxy) phenyl-1, 2 dioxetane disodium salt (AMPPD) contained in the substrate solution is dephosphorylated by the catalysis of alkaline phosphatase indirectly conjugated to particles. Luminescence (at a maximum wavelength of 477 nm) is generated by the cleavage reaction of dephosphorylated AMPPD. The luminescent signal reflects the amount of beta-amyloid 1-40 in the sample.(Package insert: Lumipulse G B-Amyloid 1-40. Fujirebio Inc; 05/2022)

 

beta-Amyloid 1-42:

The Lumipulse G beta-amyloid 1-42 is an assay system for the quantitative measurement of beta-amyloid 1-42 in CSF specimens based on CLEIA technology by a specific two-step sandwich immunoassay method on the Lumipulse G System. The specimen and biotinylated antibody solution are both added to the antibody coated particle solution. The beta-amyloid 1-42 in the specimen specifically binds to anti-beta-amyloid 1-42 monoclonal mouse antibody on the particles and biotinylated mouse antibody. Biotinylated antibody-antigen immuno-complexes are formed. The particles are washed and rinsed to remove unbound materials. Alkaline phosphatase labeled streptavidin specifically binds to biotinylated immuno-complexes on the particles. The particles are washed and rinsed to remove unbound materials. Substrate solution is added and mixed with the particles. AMPPD contained in the substrate solution is dephosphorylated by the catalysis of alkaline phosphatase indirectly conjugated to particles. Luminescence (at a maximum wavelength of 477 nm) is generated by the cleavage reaction of dephosphorylated AMPPD. The luminescent signal reflects the amount of beta-amyloid 1-42 present in the sample.(Package insert: Lumipulse G B-Amyloid 1-42. Fujirebio Inc; 05/2022)

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.

Monday

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 7 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 has been cleared, approved, or is exempt by the US Food and Drug Administration and is used per manufacturer's instructions. Performance characteristics were verified by Mayo Clinic in a manner consistent with CLIA requirements.

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

LOINC® Information
Provides guidance in determining the Logical Observation Identifiers Names and Codes (LOINC) values for the order and results codes of this test. LOINC values are provided by the performing laboratory.

Test Id Test Order Name Order LOINC Value
AMYR Beta-Amyloid Ratio (1-42/1-40), CSF In Process
Result Id Test Result Name Result LOINC Value
Applies only to results expressed in units of measure originally reported by the performing laboratory. These values do not apply to results that are converted to other units of measure.
4240R Beta-Amyloid Ratio 98485-6
AMYIN Beta-Amyloid Ratio Interpretation 69048-7

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

Test Update Resources

Change Type Effective Date
New Test 2022-07-25