26623 Precivity AD2, Reflex to Apolipoprotein E, Plasma (AD2AR)

​​​​AB42/40 Ratio; Alzheimer's; ​Amyloid Beta; Amyloid Probability Score2; APOE; Dementia; Mild cognitive impairment; p-tau217; p-tau217 Ratio; Percent p-tau217; %p-tau217; C2N​

​The PrecivityAD2 blood test measures amyloid beta (Abeta) 42/40 ratio and percent tau phosphorylated at threonine-217 (%p-tau217). The results are then combined and used in a proprietary statistical algorithm to calculate the Amyloid Probability Score 2 (APS2). The APS2, Abeta 42/40 ratio and %p-tau217 are reported, however, individual Abeta42, Abeta40, phosphorylated tau217 and non-phosphorylated tau217 concentrations are not reported. For patients who receive a positive PrecivityAD2 test result, additional testing is performed to measure the apolipoprotein E isoforms E2, E3, and E4.

​Assisting in the evaluation of adult patients, aged 55 years and older, with signs or symptoms of mild cognitive impairment or dementia who are being assessed for Alzheimer disease and other causes of cognitive decline

Determining APOE E4 status to aid in medical management and treatment decis​ions when the PrecivityAD2 blood test result is positive

This test is not intended for patients younger than 55 years, or for use as a screening test in patients without signs or symptoms of cognitive, or for serial testing for assessment of longitudinal changes.

​Contact Lab Specimen Processing at 715-221-6220 or 800-222-5835 to obtain special aliquot tubes (See Step 2 below).

1. Centrifuge within two hours of collection.

2. Label two 2-mL screw-cap micro tubes. (Screw cap micro tube, 2 mL, PCR Performance Tested, Low protein-binding (T983))

3. Aliquot 1.5 mL of plasma into each labeled micro tube.

4. Freeze plasma (no longer than 2 hours after collection) at or below -20 degrees C.

5. Place labeled aliquot tubes inside a larger tube or vial for transport.

6. Specimens must be shipped frozen on dry ice.

Gross hemolysis; Gross lipemia; Gross icterus; Outside of age range; Specimen collected outside of testing range (too long in storage before arrival to testing facility); Insufficient volume; Incorrect labeling

​​This test is not a standalone test; positive or negative Amyloid Probability Score 2 (APS2) values alone neither rule in nor rule out a diagnosis of Alzheimer disease (AD).​

Test results should be used in conjunction with other diagnostic tools such as neurological examination, neurobehavioral tests, imaging, and routine laboratory tests.

False-positive and false-negative test results may occur.

This test uses interpretive data that were derived from clinical studies in a predominantly White US population of patients with mild cognitive impairment or early dementia. The extent of the differences in results (if any) based on individuals of other racial and ethnic groups has not yet been firmly established.

Currently, there is insufficient evidence to support serial testing for the assessment of longitudinal changes in biomarkers, including monitoring response to therapy.

The results of other analyte tests using other methodologies cannot be interpreted in the context of the PrecivityAD2 test.

Apolipoprotein E

This test detects only peptides from E2, E3 and E4 proteins and does not detect peptides from rare apolipoprotein E (ApoE) phenotypes.

Although multiple epidemiological studies of diverse ethnic populations have demonstrated increased frequency of the E4 allele in late-onset AD cohorts, the extent of differences in individual risk estimates across different ethnicities has not been established.

The E4 allele is neither necessary nor sufficient for the development of AD; thus, ApoE isoform/APOE allele status cannot be used alone for the diagnosis of AD.

​Alzheimer disease (AD) is defined pathologically by the presence of amyloid plaques and neurofibrillary tangles in the brain. Clinical characteristics include gradual onset of Mild cognitive impairment (MCI), behavioral changes such as apathy, withdrawal, or agitation, and disease progression to middle and later stage dementia. Currently, no test detects AD with 100% accuracy; definitive diagnosis occurs at brain autopsy.​

Recent availability of anti-amyloid therapies increases the importance of detection of AD at an early stage. MCI impacts 12% to 18% of people in the United States over age 60 and is often an initial clinical sign of AD. Establishing or excluding an AD diagnosis with a high degree of certainty at first signs of memory decline may optimize medical management.

Brain amyloid pathology is detectable by amyloid positron emission tomography (PET) scan, cerebrospinal fluid testing, or liquid chromatography tandem mass spectrometry blood biomarker testing with high sensitivity and specificity in patients with MCI and early dementia. In all testing modalities, healthcare providers interpret test results in the context of the patient's clinical findings and other clinical work-up, as the neuropathological changes associated with AD can be seen in other forms of dementia and in unaffected individuals.

The PrecivityAD2 test is an analytically and clinically validated blood test that aids healthcare providers in ruling in or ruling out AD in patients presenting with MCI or dementia. This evaluation simultaneously quantifies specific plasma amyloid beta (Abeta) and tau peptide concentrations to calculate the Abeta42/40 ratio and percent tau phosphorylated at threonine-217 (% p-tau217). The inclusion of plasma analyte ratios has been shown to mitigate the effects of confounding factors such as chronic kidney disease. The ratios are combined into a proprietary statistical algorithm to calculate the Amyloid Probability Score 2 (APS2), a numerical value ranging from 0 to 100, that determines whether a patient is positive (has high likelihood) or negative (has low likelihood) for the presence of brain amyloid plaques by amyloid PET scan.

For patients with a positive PrecivityAD2 blood test result, apolipoprotein E (ApoE) proteotyping is performed to determine APOE E4 status.

ApoE is a component of several classes of lipoprotein particles, including chylomicron remnants, very-low-density lipoprotein (VLDL), intermediate-density lipoprotein (IDL) and high-density lipoprotein (HDL) and is highly expressed in the liver and brain. The protein has seven isoforms (ApoE1-7), the most common of which are ApoE2, ApoE3 and ApoE4. ApoE isoforms are encoded by the APOE gene alleles E1-E7. The E3 allele, most frequent in all populations, has a frequency range of 50% to 90%, whereas E4 and E2 allele frequencies range from 5% to 35% and 1% to 5%, respectively.

ApoE isoforms differentially influence the buildup of amyloid beta plaques and tau neurofibrillary tangles in the brain. Determination of APOE proteotype/genotype status may aid in clinical evaluation for AD in symptomatic patients and can inform decision-making for optimal treatment pathways. In recent clinical trials for amyloid-reducing therapies, the E4 allele showed an association with the development of amyloid-related imaging abnormalities (ARIA): cerebral edema (ARIA-E), and cerebral microhemorrhages (ARIA-H).

​​The Amyloid Probability Score 2 (APS2) result is a composite score ranging from 0 to 100 that demonstrates the strongest correlation with brain amyloid pathology compared to the individual biomarkers (amyloid beta [Abeta] 42/40 ratio or percent tau phosphorylated at threonine-217 [%p-tau217]), considered separately. Discordance of the individual biomarkers can occur.​

Table 1. Amyloid Probability Score and Interpretation

For apolipoprotein E (ApoE) testing, there are six possible allele combinations for AD risk interpretation.

ApoE proteotyping determines which ApoE protein types are present in the submitted sample. The protein types detected determine the presence of E2, E3, and/or E4 alleles, corresponding to the patient's APOE genotype (see Table 2).

Table 2. Proteotype Interpretation