Clinical Information

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.(1,2) 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.(3-5) MCI impacts 12% to 18% of people in the United States over age 60 and is often an initial clinical sign of AD.(6) 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.(7-12) 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.(7,8,13)

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).(12) The inclusion of plasma analyte ratios has been shown to mitigate the effects of confounding factors such as chronic kidney disease.(14,15) 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.(16) 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.(17)

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.(18-21) 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).(3,4)