Test Code ADEVL Alzheimer Disease Evaluation, Spinal Fluid
Specimen Required
Supplies:
Alzheimer's Disease Evaluation (ADEVL) Collection Kit (T836)
CSF AD Biomarker Tubes (T833; also included in T836)
Container/Tube:
Preferred: Sarstedt CSF False Bottom Tube 63.614.625 (2.5 mL)
Acceptable: Sarstedt 72.703.600 (1.5 mL) or Sarstedt 72.694.600 (2 mL)
Specimen Volume: 1.5 to 2.5 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.*
3. Send CSF specimen in original collection tube. Do not aliquot.
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.
4. Collection instructions can also be found on Spinal Fluid Specimen Collection Instructions for Alzheimer Disease Evaluation (T967).
Useful For
Assessment of adults with cognitive impairment being evaluated for Alzheimer disease and other causes of cognitive impairment
These assays should not be used to predict the development of dementia or other neurologic conditions or to monitor response to therapies.
Method Name
Electrochemiluminescent Immunoassay (ECLIA)
Reporting Name
Alzheimer's Disease Evaluation, CSFSpecimen Type
CSFSpecimen Minimum Volume
See Specimen Required
Specimen Stability Information
Specimen Type | Temperature | Time | Special Container |
---|---|---|---|
CSF | Refrigerated (preferred) | 14 days | BlueTop SARSTEDT |
Frozen | 60 days | BlueTop SARSTEDT | |
Ambient | 12 hours | BlueTop SARSTEDT |
Reject Due To
Gross hemolysis | Reject |
Gross lipemia | OK |
Gross icterus | Reject |
Clinical Information
Two neuropathologic features observed in the brain of patients with Alzheimer disease (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 (amyloid-PET) to visualize the presence of amyloid lesions in the cerebral cortex is available in some specialized centers. Measuring Abeta42 peptides and certain phosphorylated Tau (such as p-Tau181) proteins in cerebrospinal fluid (CSF) may be used as a means to assess the presence of amyloid pathology. In particular, the use of the p-Tau181/Abeta42 ratio has been shown to be an excellent surrogate marker of amyloid plaque burden, caused by increased deposition of beta-amyloid 1-42 in the brain. 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 Research Framework.
The CSF assays included in this evaluation are beta-amyloid (1-42; Abeta42), total Tau (t-Tau), and phosphorylated Tau (p-Tau181).
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. 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-messenger RNA. 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 hyperphosphorylated Tau proteins called p-Tau. The p-Tau assay detects phosphorylated Tau at threonine 181 (p-Tau181).
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 are 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 appropriate use criteria 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 who are considered 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 (younger than 65 years)
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.
Reference Values
Beta-amyloid (1-42) (Abeta42): >834 pg/mL
Total-Tau: ≤238 pg/mL
Phosphorylated-Tau 181: ≤21.6 pg/mL
p-Tau/Abeta42: ≤0.028
Interpretation
A beta-amyloid (1-42; Abeta42) result greater than 834 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 834 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-Tau181) 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-Tau181 concentration of less than or equal to 238 pg/mL and less than or equal to 21.6 pg/mL, respectively, reduces the likelihood that a patient's cognitive impairment is due to AD.
The use of p-Tau181/Abeta42 ratio provides better concordance with amyloid PET scan when compared to Abeta42, p-Tau181, and t-Tau individually. The p-Tau/Abeta42 ratio provides better concordance with amyloid PET imaging when compared to Abeta42, phospho-Tau and total-Tau individually. A cut-off of 0.028 provides optimal balance between negative percent agreement (NPA) and positive percent agreement (PPA) when compared to amyloid PET results. A p-Tau/Abeta42 ratio of 0.028 or less has a 92% NPA with normal amyloid PET. A ratio above 0.028 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 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-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 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 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-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 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 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 disease. |
This table and interpretations are based on the National Institute on Aging and Alzheimer's Association research framework diagnostic recommendations.
Day(s) Performed
Tuesday, Thursday, Friday
Report Available
1 to 4 daysSpecimen Retention Time
12 monthsPerforming Laboratory
Mayo Clinic Laboratories in RochesterTest Classification
This test has been modified from the manufacturer's instructions. Its performance characteristics were 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
83520 x 3
LOINC Code Information
Test ID | Test Order Name | Order LOINC Value |
---|---|---|
ADEVL | Alzheimer's Disease Evaluation, CSF | 104134-2 |
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.