PrecivityAD2™ Blood Test: Analytical Validation of an LC-MS/MS Assay for Quantifying Plasma Phospho-tau217 and Non-Phospho-tau217 Peptide Concentrations That Are Used with Plasma Amyloid-β42/40 in a Multianalyte Assay with Algorithmic Analysis for Detecting Brain Amyloid Pathology.

Alzheimer's disease (AD) is a progressive irreversible neurodegenerative disorder that represents a major global public health concern. Traditionally, AD is diagnosed using cerebrospinal fluid biomarker analysis or brain imaging modalities. Recently, less burdensome, more widely available blood biomarker (BBM) assays for amyloid-beta (Aβ42/40) and phosphorylated-tau concentrations have been found to accurately identify the presence/absence of brain amyloid plaques and tau tangles and have helped to streamline AD diagnosis.

Standardization of Apolipoprotein B, LDL-Cholesterol, and Non-HDL-Cholesterol.

Concern continues about whether the measurement of apolipoprotein B (apoB) is adequately standardized, and therefore, whether apoB should be applied widely in clinical care. This concern is misplaced. Our objective is to explain why and what the term "standardization" means.

Independent study demonstrates amyloid probability score accurately indicates amyloid pathology.

Background: The amyloid probability score (APS) is the model read-out of the analytically validated mass spectrometry-based PrecivityAD blood test that incorporates the plasma Aβ42/40 ratio, ApoE proteotype, and age to identify the likelihood of brain amyloid plaques among cognitively impaired individuals being evaluated for Alzheimer's disease.

Purpose: This study aimed to provide additional independent evidence that the pre-established APS algorithm, along with its cutoff values, discriminates between amyloid positive and negative individuals.

Methods: The diagnostic performance of the PrecivityAD test was analyzed in a cohort of 200 nonrandomly selected Australian Imaging, Biomarker & Lifestyle Flagship Study of Aging (AIBL) study participants, who were either cognitively impaired or healthy controls, and for whom a blood sample and amyloid PET imaging were available.

Assessment of a Plasma Amyloid Probability Score to Estimate Amyloid Positron Emission Tomography Findings Among Adults With Cognitive Impairment.

Importance: The diagnostic evaluation for Alzheimer disease may be improved by a blood-based diagnostic test identifying presence of brain amyloid plaque pathology.

Objective: To determine the clinical performance associated with a diagnostic algorithm incorporating plasma amyloid-β (Aβ) 42:40 ratio, patient age, and apoE proteotype to identify brain amyloid status.

Design, Setting, And Participants: This cohort study includes analysis from 2 independent cross-sectional cohort studies: the discovery cohort of the Plasma Test for Amyloidosis Risk Screening (PARIS) study, a prospective add-on to the Imaging Dementia-Evidence for Amyloid Scanning study, including 249 patients from 2018 to 2019, and MissionAD, a dataset of 437 biobanked patient samples obtained at screenings during 2016 to 2019.

The PrecivityAD™ test: Accurate and reliable LC-MS/MS assays for quantifying plasma amyloid beta 40 and 42 and apolipoprotein E proteotype for the assessment of brain amyloidosis.

Background: There is an unmet need for an accessible, less invasive, cost-effective method to facilitate clinical trial enrollment and aid in clinical Alzheimer's disease (AD) diagnosis. APOE genotype affects the clearance and deposition of amyloid-beta (Aβ) with APOE4 carriers having increased risk while APOE2 alleles appear to be protective. Lower plasma Aβ42/40 correlates with brain amyloidosis.

A blood-based diagnostic test incorporating plasma Aβ42/40 ratio, ApoE proteotype, and age accurately identifies brain amyloid status: findings from a multi cohort validity analysis.

Background: The development of blood-based biomarker tests that are accurate and robust for Alzheimer's disease (AD) pathology have the potential to aid clinical diagnosis and facilitate enrollment in AD drug trials. We developed a high-resolution mass spectrometry (MS)-based test that quantifies plasma Aβ42 and Aβ40 concentrations and identifies the ApoE proteotype. We evaluated robustness, clinical performance, and commercial viability of this MS biomarker assay for distinguishing brain amyloid status.

Lipoprotein(a) particle number assay without error from apolipoprotein(a) size isoforms.

Background: Lipoprotein(a) [Lp(a)] is an important cardiovascular risk factor, but clinical immunoassays are flawed. Apolipoprotein(a) [apo(a)], the characteristic protein of Lp(a), contains a variable number of kringle repeats (size isoforms) that make accurate measurement of Lp(a) difficult. We developed a sandwich enzyme immunoassay that uses a murine monoclonal anti-apo(a) antibody for capture and a polyclonal anti-apolipoprotein B (apo B) for detection.

Comparability of Lipoprotein Particle Number Concentrations Across ES-DMA, NMR, LC-MS/MS, Immunonephelometry, and VAP: In Search of a Candidate Reference Measurement Procedure for apoB and non-HDL-P Standardization.

Background: Despite the usefulness of standard lipid parameters for cardiovascular disease risk assessment, undiagnosed residual risk remains high. Advanced lipoprotein testing (ALT) was developed to provide physicians with more predictive diagnostic tools. ALT methods separate and/or measure lipoproteins according to different parameters such as size, density, charge, or content, and equivalence of results across methods has not been demonstrated.

Discordance analysis and the Gordian Knot of LDL and non-HDL cholesterol versus apoB.

Purpose Of Review: Conventional methods, comparing the concentration of cholesterol to particle number as indices of cardiovascular risk, have not produced consistent results, in large part, because they treat these variables as independent and unrelated. However, although highly correlated, apolipoprotein B particles may contain a normal mass of cholesterol or may be cholesterol-depleted or cholesterol-enriched. Discordance analysis compares the predictive power of LDL-C and non-HDL-C to apolipoprotein B and LDL particle numbers in patients in whom they differ, that is, in whom they are discordant.

Immunoprecipitation of apolipoprotein B-containing lipoproteins for isolation of HDL particles.

Background: Immunoprecipitation (IP) of non-HDL particles with antisera provides the simplest and most specific method available for the separation of HDL. We compared the LipoSep™ IP reagent with the dextran sulfate/MgCl2 precipitation method (DS).

Methods: The IP reagent (200 μl) was added to an equal volume of serum, vortexed, incubated for 10 min at room temperature, and microcentrifuged at 12,000 rpm for 10 min.

Association of apolipoprotein B and nuclear magnetic resonance spectroscopy-derived LDL particle number with outcomes in 25 clinical studies: assessment by the AACC Lipoprotein and Vascular Diseases Division Working Group on Best Practices.

Background: The number of circulating LDL particles is a strong indicator of future cardiovascular disease (CVD) events, even superior to the concentration of LDL cholesterol. Atherogenic (primarily LDL) particle number is typically determined either directly by the serum concentration of apolipoprotein B (apo B) or indirectly by nuclear magnetic resonance (NMR) spectroscopy of serum to obtain NMR-derived LDL particle number (LDL-P).

Content: To assess the comparability of apo B and LDL-P, we reviewed 25 clinical studies containing 85 outcomes for which both biomarkers were determined.

Reliability of low-density lipoprotein cholesterol, non-high-density lipoprotein cholesterol, and apolipoprotein B measurement.

There is little understanding of the reliability of laboratory measurements among clinicians. Low-density lipoprotein cholesterol (LDL-C) measurement is the cornerstone of cardiovascular risk assessment and prevention, but it is fraught with error. Therefore, we have reviewed issues related to accuracy and precision for the measurement of LDL-C and the related markers non-high-density lipoprotein cholesterol (non-HDL-C) and apolipoprotein B.

A meta-analysis of low-density lipoprotein cholesterol, non-high-density lipoprotein cholesterol, and apolipoprotein B as markers of cardiovascular risk.

Background: Whether apolipoprotein B (apoB) or non-high-density lipoprotein cholesterol (HDL-C) adds to the predictive power of low-density lipoprotein cholesterol (LDL-C) for cardiovascular risk remains controversial.

Methods And Results: This meta-analysis is based on all the published epidemiological studies that contained estimates of the relative risks of non-HDL-C and apoB of fatal or nonfatal ischemic cardiovascular events. Twelve independent reports, including 233 455 subjects and 22 950 events, were analyzed.

Why is non-high-density lipoprotein cholesterol a better marker of the risk of vascular disease than low-density lipoprotein cholesterol?

Low-density lipoprotein cholesterol (LDL-C) has been the focus of managing lipoprotein disorders for decades. It is now time to consider a change. Both apolipoprotein B (apoB) and non-high-density lipoprotein cholesterol (HDL-C) have been shown to be more accurate markers of cardiovascular risk than LDL-C.

Apolipoprotein B and cardiovascular disease risk: position statement from the AACC Lipoproteins and Vascular Diseases Division Working Group on Best Practices.

Background: Low-density lipoprotein cholesterol (LDL-C) has been the cornerstone measurement for assessing cardiovascular risk for nearly 20 years.

Content: Recent data demonstrate that apolipoprotein B (apo B) is a better measure of circulating LDL particle number (LDL-P) concentration and is a more reliable indicator of risk than LDL-C, and there is growing support for the idea that addition of apo B measurement to the routine lipid panel for assessing and monitoring patients at risk for cardiovascular disease (CVD) would enhance patient management. In this report, we review the studies of apo B and LDL-P reported to date, discuss potential advantages of their measurement over that of LDL-C, and present information related to standardization.

Carbohydrate restriction and dietary cholesterol distinctly affect plasma lipids and lipoprotein subfractions in adult guinea pigs.

To evaluate the effects of carbohydrate restriction (CR) and dietary cholesterol on lipoprotein metabolism, adult male guinea pigs (10 guinea pigs/diet) were fed either low (0.04 g/100 g) or high (0.25 g/100 g) amounts of dietary cholesterol, in combination with either low (10% total energy) or high (54.

Clinical utility of different lipid measures for prediction of coronary heart disease in men and women.

Context: Evidence is conflicting regarding the performance of apolipoproteins vs traditional lipids for predicting coronary heart disease (CHD) risk.

Objectives: To compare performance of different lipid measures for CHD prediction using discrimination and calibration characteristics and reclassification of risk categories; to assess incremental utility of apolipoproteins over traditional lipids for CHD prediction.

Design, Setting, And Participants: Population-based, prospective cohort from, Framingham, Massachusetts.

Change in plasma lutein after egg consumption is positively associated with plasma cholesterol and lipoprotein size but negatively correlated with body size in postmenopausal women.

We investigated associations between plasma concentrations of cholesterol and lutein after consumption of eggs. Using a crossover design, 22 postmenopausal women (50-77 y) consumed an egg treatment (640 mg/d additional cholesterol and 600 mug/d additional lutein + zeaxanthin) or a baseline treatment (no additional cholesterol or lutein + zeaxanthin) for 30 d, followed by a 3-wk washout period and the alternate diet. The increases in plasma total cholesterol and lutein due to egg consumption were related (r = 0.

A combination therapy including psyllium and plant sterols lowers LDL cholesterol by modifying lipoprotein metabolism in hypercholesterolemic individuals.

We conducted a randomized, double blind, crossover, placebo-controlled study to determine the effects of a combination therapy including plant sterols (PS) and psyllium (PSY), provided via cookies, on plasma lipids and on the size and subfraction distribution of VLDL, LDL, and HDL. Thirty-three healthy free-living individuals (11 males and 22 females), aged 35-65 y, with a BMI between 25 and 35 kg/m(2) and initial plasma LDL cholesterol (LDL-C) concentrations between 2.6 and 4.

Relationship between plasma carotenoids and prostate cancer.

Carotenoids, particularly lycopene, are thought to decrease prostate cancer risk, but the relationship between plasma carotenoid concentrations and risk in various populations has not been well characterized. Comparing 118 non-Hispanic Caucasian men mainly from southeast Texas with nonmetastatic prostate cancer with 52 healthy men from the same area, we conducted a case-control analysis evaluating associations between risk and plasma levels of total carotenoids, beta-cryptoxanthin, alpha- and trans-beta-carotene, lutein and zeaxanthin, total lycopenes, trans-lycopene, total cis-lycopenes, and cis-lycopene isoforms 1, 2, 3, and 5. Risk for men with high plasma levels of alpha-carotene, trans-beta-carotene, beta-cryptoxanthin, and lutein and zeaxanthin was less than half that for those with lower levels.

Dietary carbohydrate and cholesterol influence the number of particles and distributions of lipoprotein subfractions in guinea pigs.

Guinea pigs (n=10/group) were fed one of three diets: a high carbohydrate (CHO) (42% energy), low cholesterol (0.04%) diet (LChHC), a diet with the same amount of CHO but with 0.25% cholesterol (HChHC) or a diet with 11% of energy from CHO and 0.

Carbohydrate restriction alters lipoprotein metabolism by modifying VLDL, LDL, and HDL subfraction distribution and size in overweight men.

To determine the effects of carbohydrate restriction (CR) with and without soluble fiber on lipoprotein metabolism, 29 men participated in a 12-wk weight loss intervention. Subjects were matched by age and BMI and randomly assigned to consume 3 g/d of either a soluble fiber supplement (n=14) or placebo (n=15) with a macronutrient energy distribution of approximately 10% carbohydrate, approximately 65% fat, and approximately 25% protein. Because the groups did not differ in any of the variables measured, all data were pooled and comparisons were made between baseline and 12 wk.