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Test ID: ADEVL Alzheimer Disease Evaluation, Spinal Fluid


Specimen Required


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: CSF AD Biomarker Tube; specimens not collected in this tube will be rejected

Specimen Volume: 2 mL

Collection Instructions:

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

2. Collect 2 mL of CSF directly into CSF AD Biomarker Tube. Do not aliquot. Analysis needs to be performed using collection tube.


Useful For

Assessment of adults with cognitive impairment being evaluated for Alzheimer disease (AD) and other causes of cognitive impairment.

Method Name

Electrochemiluminescent Immunoassay

Reporting Name

Alzheimer's Disease Evaluation, CSF

Specimen Type

CSF

Specimen Minimum Volume

See Specimen Required

Specimen Stability Information

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

Clinical Information

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 brains of patients with AD 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 FDA-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 six 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 hyper-phosphorylation and developed aggregates of hyper-phosphorylated Tau proteins called p-Tau. The p-Tau assay detects phosphorylated 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.

Reference Values

Abeta42: >1026 pg/mL

Total-Tau: ≤238 pg/mL

Phospho-Tau 181: ≤21.7 pg/mL

p-Tau/Abeta42: ≤0.023

Interpretation

An 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 (-)

Phospho Tau (-)

Total Tau (-)

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

Abeta42 (+)

phospho-Tau (-)

total-Tau (-)

Abnormal Abeta42 concentrations are present in CSF.

Phospho-Tau and total-Tau concentrations are normal.

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

Abeta42 (+)

phospho-Tau (+)

total-Tau (-)

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

The total-Tau concentration is normal.

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

Abeta42 (+)

phospho Tau (+)

total Tau (+)

Abnormal Abeta42, phospho-Tau and total-Tau concentrations are present in CSF. These results are consistent with the presence of Alzheimer's disease.

Abeta42 (+)

phospho Tau (-)

total Tau (+)

Abnormal Abeta42, and total-Tau concentrations are present in CSF.

The phospho-Tau concentration is normal.

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

Abeta42 (-)

phospho-Tau (+)

total-Tau (-)

Abnormal phospho-Tau concentrations are present in CSF.

Abeta42 and total-Tau concentrations are normal.

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

Abeta42 (-)

phospho tau (-)

total-Tau (+)

Abnormal total-Tau concentrations are present in CSF.

The Abeta42 and phospho-Tau concentrations are normal.

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

Abeta42 (-)

phospho-Tau (+)

total-Tau (+)

Abnormal phospho-Tau and total-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 National Institute on Aging and Alzheimer's Association research framework diagnostic recommendations.(See Jack CR Jr. et al: Alzheimers. Dement. 2018;14:535-562)

Clinical Reference

1. 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

2. 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

3. 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

4. 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

Day(s) and Time(s) Performed

Tuesday, 6 p.m.

Analytic Time

1 day

Test Classification

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 U.S. Food and Drug Administration.

CPT Code Information

83520 x 3

LOINC Code Information

Test ID Test Order Name Order LOINC Value
ADEVL Alzheimer's Disease Evaluation, CSF In Process

 

Result ID Test Result Name Result LOINC Value
PTABR p-Tau/Abeta42 41027-4
ADINT AD Interpretation 69048-7
AB42P Abeta42 33203-1
TTAUP Total-Tau 30160-6
PTAUP Phospho-Tau(181P) 72260-3

Forms

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