José Antonio Allué (Spain)
ARACLON Biotech
Mass Spectrometry Laboratory
Ph.D. (Pharmacy) University of Barcelona, Spain. Almost twenty-five years in the field of Biological Mass Spectrometry, fourteen of them dedicated to research in Alzheimer´s Disease by HPLC and MS (MALDI, IMS-MS, Orbitrap-MS, reTOF-MS, TOF/TOF-MS, Ion-Trap-MS and Triple Quadrupole-MS). Applications of both, targeted and untargeted, proteomic techniques in the fields of immunology, metabolism, pharmacokinetics and pharmacodynamics. Applications of High-Mass MALDI Mass Spectrometry for the analysis of protein complexes and vaccines. Label-free shotgun proteomics by Travelling Wave Ion Mobility Spectrometry coupled to TOF-MS. Applications of MS to the study of amyloid species in tissues and biofluids, including human, dog and transgenic mice models. Research focus: blood and cerebrospinal fluid amyloid biomarkers in Alzheimer´s Disease. Direct analysis of amyloid peptides in blood without immunoprecipitation enrichment.

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PLASMA AΒ42/AΒ40 MEASURED BY A NOVEL MASS-SPECTROMETRIC METHOD IDENTIFIES EARLY AMYLOID DEPOSITION IN INDIVIDUALS AT RISK OF ALZHEIMER’S DISEASE (FACEHBI COHORT)

Session Name
1650 - FLUID BIOMARKERS 5 (ID 81)
Session Type
SYMPOSIUM
Date
Sat, 19.03.2022
Session Time
02:45 PM - 04:45 PM
Room
ONSITE: 114
Lecture Time
03:00 PM - 03:15 PM
Presenter

Abstract

Aims

To assess the ability of plasma Aβ42/Aβ40 ratio as determined by a novel antibody-free HPLC-MS/MS method (ABtest-MS, Araclon Biotech) to detect early brain Aβ deposition in individuals at risk of Alzheimer’s disease (AD).

Methods

We have developed a unique method that quantifies Aβ40 and Aβ42 directly from plasma. Since no immunoprecipitation or enzymatic digestion steps are required, sample preparation time and cost are drastically reduced. A comprehensive analytical validation was performed.

Aβ40 and Aβ42 plasma levels were measured with ABtest-MS in 200 individuals with subjective cognitive decline from the Fundació ACE Healthy Brain Initiative (FACEHBI) cohort. Participants underwent comprehensive neurological evaluation and cognitive testing, APOE genotyping and 18F-florbetaben (FBB)-PET brain imaging. Cutoff for early Aβ-PET positivity was established at >13.5 centiloids (CL).

The ability of plasma Aβ42/Aβ40 to detect early Aβ-PET positivity was determined with logistic regression models and ROC curve analysis.

Results

Aβ42/Aβ40 plasma ratio showed a significant negative correlation with FBB-PET CL values (rho=-0.390; p=1.16e-08). Additionally, Aβ-PET(+) individuals presented lower Aβ42/Aβ40 levels than subjects in the Aβ-PET(-) group (p=5.93e-12).

Aβ42/Aβ40 plasma ratio detected abnormal brain Aβ status with AUC of 0.87 and accuracy of 82%. After adjusting for age, sex and APOE4 genotype, AUC further improved to 0.89.

Conclusions

This novel ABtest-MS method accurately identifies early amyloid deposition in individuals at risk of AD. On-going analysis of the follow-up visits of the FACEHBI cohort will assess the ability of baseline Aβ42/Aβ40 plasma ratio as measured with ABtest-MS to predict future conversion to mild cognitive impairment and/or dementia.

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