Blood Derived Amyloid Biomarkers for Alzheimer’s Disease Prevention - 21/11/24

Doi : 10.14283/jpad.2021.70 
C. Udeh-Momoh 1, 2, B. Zheng 1, A. Sandebring-Matton 1, 2, 3, G. Novak 4, M. Kivipelto 1, 2, 5, 6, L. Jönsson 3, Lefkos Middleton, Prof. 1, 7,

Alzheimer’s Disease Neuroimaging Initiative

1 Ageing Epidemiology Research Unit, School of Public Health, Faculty of Medicine, Imperial College London, W6 8RP, London, UK 
2 Division of Clinical Geriatrics, Center for Alzheimer Research, Department of Neurobiology, Care Sciences and Society, Karolinska Institutet, Stockholm, Sweden 
3 Division of Neurogeriatrics, Department of Neurobiology, Care Sciences and Society, Karolinska Institutet, Stockholm, Sweden 
4 Janssen Research & Development, LLC, Titusville, USA 
5 Public Health Promotion Unit, National Institute for Health and Welfare (THL), Helsinki, Finland 
6 Institute of Clinical Medicine, Neurology, University of Eastern Finland, Kuopio, Finland 
7 Public Health Directorate, Imperial College NHS Healthcare Trust, London, UK 

g l.middleton@imperial.ac.uk l.middleton@imperial.ac.uk

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Abstract

Background

Reliable, widely accessible and affordable biomarkers for predicting Alzheimer’s disease (AD) brain pathology status are a necessity to aid development of prevention strategies in cognitively healthy at-risk older adults, at the right timepoint. Measurements of the key neuropathological hallmark beta-amyloid (Aβ) by PET neuroimaging or cerebrospinal fluid measures reflect its accumulation in the brain, yet recent methodological advancements now enable blood-based measures reflecting cerebral amyloid burden.

Objectives

The current study validated the capacity of plasma Aβ42/Aβ40 measured using six different assays to predict amyloid positivity in a subgroup of cognitively unimpaired (CU) participants in the ADNI study and assessed its ability to discriminate CU from AD cases. We also explored economic viability of using two different plasma amyloid assays for pre-screening in AD prevention trials and as routine clinical diagnostic tool, versus amyloid PET alone.

Design

A cross-sectional analysis of plasma and brain amyloid data, including comparative cost analysis of the plasma biomarkers in relation to brain amyloid PET.

Setting

Alzheimer’s Disease Neuroimaging Initiative (ADNI).

Participants

ADNI participants consisting of 115 CU, mild cognitive impairment and AD cases who had plasma Aβ42/ Aβ40 measured with six platforms.

Measurements

Plasma Aβ42/Aβ40 was measured via six different platforms: three immunoassays (Roche, Quanterix and ADx Neurosciences) and three mass spectrometry (MS) based assays (WashU, Shimadzu and Gothenburg). Aβ-PET imaging was conducted within three months of plasma sampling using [18F]florbetapir.

Results

There was a weak to moderate correlation of plasma Aβ42/Aβ40 ratio between platforms. The MS-based WashU test had the highest capacity to discriminate between CU and AD (area under the curve, AUC = 0.734, 95% CI: 0.613–0.854; P = 0.008). Within the CU group, the WashU plasma amyloid test had the best discriminative capacity to distinguish Aβ+ from Aβ- (AUC = 0.753, 95% CI: 0.601–0.905; P = 0.003) closely followed by the immunoassay from Roche (AUC = 0.737, 95% CI: 0.597–0.877; P = 0.006). The exploratory economic analyses showed that the use of Roche or WashU plasma amyloid assay as a pre-screening tool prior to Aβ-PET scans for clinical trial recruitment significantly reduced total screening cost (saving up to $5882 per recruited patient) expected in an AD prevention trial.

Conclusions

With few available treatment strategies, dementia prevention is a global priority. CU individuals at risk for AD are the target population for dementia prevention but have been poorly studied. Our findings confirming diagnostic value of ultrasensitive immunoassays and high-performance immunoprecipitation coupled with MS for measurement of plasma Aβ42/β40 to detect PET amyloid positivity in CU participants allude to potential clinical utility of this biomarker. Plasma Aβ42/Aβ40 could be optimal for pre-selecting at-risk candidates for more invasive and expensive investigations across AD prevention clinical trials and clinical care for a rapidly ageing population.

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Key words : Plasma Aβ42/Aβ40, diagnostic biomarker, AD prevention, cognitively unimpaired, economic analysis


Mappa


 co-first authors
Data used in preparation of this article were obtained from the Alzheimer’s Disease Neuroimaging Initiative (ADNI) database (adni.loni.usc.edu). As such, the investigators within the ADNI contributed to the design and implementation of ADNI and/or provided data but did not participate in analysis or writing of this report. A complete listing of ADNI investigators can be found at: ADNI_Acknowledgement_List.pdf


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Vol 9 - N° 1

P. 12-21 - Gennaio 2022 Ritorno al numero
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