Evaluation of two plasma‐based proteotyping assays against APOE ε4 genotyping in a memory clinic setting: The Gothenburg H70 Clinical Studies
Year: 2025
Type: article
Abstract: INTRODUCTION: Apolipoprotein E (APOE) ε4 allele status is associated with an increased risk of Alzheimer's disease and should be determined prior to initiation of anti-amyloid beta antibody treatment, because of increased risk of treatment-related side effects. Plasma-based apoE4 proteotyping may be an alternative to genotyping, with limited clinical evidence. METHODS: apoE4 proteotyping was performed on 164 memory-clinic patients, using one chemiluminescent enzyme immunoassay (CLEIA) and one nucleic acid-linked immunosandwich assay (NULISA). The assays were evaluated against APOE ε4 blood genotyping. RESULTS: The CLEIA had a 100% sensitivity and 98.5% specificity to classify APOE ε4 homozygosity and carriership in relation to genotyping. The NULISA had a 92.9% sensitivity and 97.1% specificity to classify homozygosity and a 100% sensitivity and 98.5% specificity to classify carriership. DISCUSSION: The high performance suggests that the assays may be used as an easily available tool for identifying individuals for definitive APOE ε4 genotyping in a two-step approach. HIGHLIGHTS: Plasma-based proteotyping presented good to excellent sensitivity in identifying apolipoprotein E (APOE) ε4 homozygosity. The negative predictive value was also very good to excellent, allowing us to rule out APOE ε4 homozygosity with high precision. Assays with excellent precision show potential for identifying individuals for definitive APOE ε4 genotyping in a two-step approach.
Source: Alzheimer s & Dementia
DOI: 10.1002/alz.14610
Institutions: Sahlgrenska University Hospital, Region Västra Götaland, University of Gothenburg, University of Science and Technology of China, Sorbonne Université, Institut des Sciences Moléculaires, Pitié-Salpêtrière Hospital, Institut du Cerveau, University of Arizona, Banner Sun Health Research Institute, Banner Alzheimer’s Institute, University of Wisconsin System, University of Wisconsin–Madison, UK Dementia Research Institute, UCL Queen Square Institute of Neurology, University College London
Language: English
Subfield: Physiology
Field: Medicine
Domain: Health Sciences
Open Access status: hybrid
Estimated APC paid: $4,200
Funders: Alzheimer's Association, Alzheimer's Drug Discovery Foundation, Familjen Erling-Perssons Stiftelse, Cure Alzheimer's Fund, Stiftelsen för Gamla Tjänarinnor, EU Joint Programme – Neurodegenerative Disease Research, European Partnership on Metrology, National Institute for Health and Care Research, University College London, European Commission, Hjärnfonden, Vetenskapsrådet, Norges Forskningsråd, Sahlgrenska Universitetssjukhuset, Göteborgs Universitet, Konung Gustaf V:s och Drottning Victorias Frimurarestiftelse, Forskningsrådet om Hälsa, Arbetsliv och Välfärd, Kirsten og Freddy Johansens Fond, Stiftelsen Psykiatriska Forskningsfonden, Alzheimerfonden, University College London Hospitals NHS Foundation Trust, UK Dementia Research Institute, Olav Thon Stiftelsen, Fondation pour la Recherche sur Alzheimer, Horizon 2020 Framework Programme, HORIZON EUROPE Framework Programme, UCLH Biomedical Research Centre, National Institute on Aging, H2020 Marie Skłodowska-Curie Actions
Awards: G103279721, G1075922514, G1088883541, G1101619023, G1111228157, G1135383168, G1172252064, G1186540381, G1222782219, G1307223927, G1307999793, G1311708188, G1343867371, G1346957673, G1407244959, The Alzheimer’s Association quality control (QC) program for CSF and plasma biomarkers - Continuation, G150733400, G1546555014, G1588116593, G1618790837, G1710774808, G1714203265, G172399529, G1740841696, G1771944843, G1776849529, G1802301745, G180825096, G1833008592, Understanding Alzheimer Blood Biomarkers for Tau Pathology, G1928552717, G1938858119, G196098375, G1964879736, G201353144, G2081597990, G2104793998, G2189472788, G2224941001, G2237966762, G2239926140, G2252188508, G2256555670, G2263584233, G237833635, G2385484910, G2434909840, Mental and cognitive health in relation to functional ability and somatic health in the elderly. The influence of age, sex, birth cohort, genetic, psychological, social and neurobiological factors, G2501682398, G2521197280, G2533889179, G2543812357, G2634670634, G2704608434, G2804859505, G2826876974, G284702637, G292763017, G2977151936, Trajectories of neuronal degeneration and vascular pathology in preclinical Alzheimer`s disease, G3027168043, G3040676140, G3041725664, G308275008, G3126964432, G313301595, Fluid biomarkers for neurodegenerative dementias, Characterization of Neuroinflammation Biomarkers in Alzheimer's disease, G3410993990, G3509189227, G3515813156, G3617411373, G3655537922, G366952799, G3809224024, G3842727039, G3914690605, G3939712136, G3978352386, G3993981701, G4010165030, G4045653179, G4166693258, G4181244686, G420145614, G4228906844, G4240516103, G4244943609, G4260843567, G429241845, G4293249722, G432431387, G434337789, G4377393254, G439911564, G4404751248, G4495868458, G4639786718, G4786159458, G4937468798, G4960203590, G4962764320, G5010915254, G5040492720, G506008078, G5063629206, G5080493730, Mental and cognitive health in relation to functional ability and somatic health in the elderly. The influence of age, sex, birth cohort, genetic, psychological, social and neurobiological factors., G5111995507, G513711111, G514254762, G516766298, G5180844870, NEAR: The National E-infrastructure for Aging Research in Sweden, G525443564, G5264190596, The baby-boomers and the new ageing. Birth cohorts born 1901-1944 are followed from age 70 to 75 regarding how physical, mental, cognitive, social, and functional ability changes with age, G5293913673, Fluid biomarkers for neurodegenerative dementias, G5576250680, G5592886007, G5619554209, G5712520100, G5777938672, G5778058681, G5782211091, G5784447569, G588761001, G590676727, Analysing the heavy element factories of the Universe : photometric and spectroscopic sample study of kilonovae, G5987387215, CASCADE: CAuSe or Consequence in Alzheimer DiseasE?, G6112088384, G6142763750, G6158734006, Multi-omics Interdisciplinary Research Integration to Address DEmentia diagnosis, G6168044258, G6196845781, G6207287561, G6252389079, G6273523062, G632030864, G6422975485, G6470304958, G6500483005, G6544145387, G6556538844, Multi-omics Interdisciplinary Research Integration to Address DEmentia diagnosis, G6714009896, Application of high power ultrasounds (HPUs) to improve the sustainability in meat TENderize and BRINe processes, G6745400708, G680319674, G691317373, G6994896833, Mental and cognitive health in the elderly. Relation to age, sex, birth cohort, functional ability, somatic health, genetic, psychological, social and neurobiological factors, G7075164165, G712881263, G7143958211, G7358480839, G753712112, G7564620063, G7735889112, G7804671150, G7907773732, G7916899675, G791739130, G7964167928, G821247696, G8286231635, G839602194, G8671169300, G8711430475, G8782684654, G8785932992, G8806732996, G8939766884, G8964722967, Arizona Alzheimer's Disease Research Center, Analysing the heavy element factories of the Universe : photometric and spectroscopic sample study of kilonovae, G92992353, G98538672
OpenAlex ID: W4407908145