A Blood Test for Alzheimer’s Disease: Progress, Challenges, and Recommendations

Issue title: Alzheimer’s Disease: New Beginnings

Guest editors: G. Perry, J. Avila, P.I. Moreira, A.A. Sorensen and M. Tabaton

Article type: Review Article

Authors: Kiddle, Steven J.^{a; b; *} | Voyle, Nicola^a | Dobson, Richard J.B.^{a; c; d; *}

Affiliations: [a] Department of Biostatistics and Health Informatics, Institute of Psychiatry, Psychology and Neuroscience, King’s College London, London, UK | [b] MRC Biostatistics Unit, Cambridge Institute of Public Health, University of Cambridge, Cambridge, UK | [c] NIHR Biomedical Research Centre for Mental Health and Biomedical Research Unit for Dementia at South London and Maudsley NHS Foundation, London, UK | [d] Farr Institute of Health Informatics Research, UCL Institute of Health Informatics, University College London, London, UK

Correspondence: [*] Correspondence to: Dr. Steven Kiddle, MRC Biostatistics Unit, Cambridge Biomedical Campus, Cambridge Institute of Public Health, Forvie Site, Robinson Way, Cambridge CB2 0SR, UK. Tel.: +44 0 1223 760717; E-mail: [email protected] and Professor Richard Dobson, MRC Social, Genetic and Developmental Psychiatry Centre, Institute of Psychiatry, Psychology and Neuroscience, King’s College London, London SE5 8AF, UK. Tel.: +44 0 20 7848 0924; E-mail: [email protected].

Abstract: Ever since the discovery of APOE ɛ4 around 25 years ago, researchers have been excited about the potential of a blood test for Alzheimer’s disease (AD). Since then researchers have looked for genetic, protein, metabolite, and/or gene expression markers of AD and related phenotypes. However, no blood test for AD is yet being used in the clinical setting. We first review the trends and challenges in AD blood biomarker research, before giving our personal recommendations to help researchers overcome these challenges. While some degree of consistency and replication has been seen across independent studies, several high-profile studies have seemingly failed to replicate. Partly due to academic incentives, there is a reluctance in the field to report predictive ability, to publish negative findings, and to independently replicate the work of others. If this can be addressed, then we will know sooner whether a blood test for AD or related phenotypes with clinical utility can be developed.

Keywords: Alzheimer’s disease, blood proteins, blood tests, cohort studies, data reporting, genetics, gene expression, metabolomics, research design

DOI: 10.3233/JAD-179904

Journal: Journal of Alzheimer's Disease, vol. 64, no. s1, pp. S289-S297, 2018