Thimet oligopeptidase as a potential CSF biomarker for Alzheimer's disease

Our previous antibody-based cerebrospinal fluid (CSF) proteomics study showed that Thimet oligopeptidase (THOP1), an amyloid beta (Aβ) neuropeptidase, was increased in mild cognitive impairment with amyloid pathology (MCI-Aβ+) and Alzheimer's disease (AD) dementia compared with controls and dem...

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Detalhes bibliográficos
Autores: Hok-A-Hin, Yanaika S.|||0000-0001-9713-116X, Bolsewig, Katharina|||0000-0003-3116-7789, Ruiters, Daimy N., Lleó, Alberto|||0000-0002-2568-5478, Alcolea, Daniel|||0000-0002-3819-3245, Lemstra, Afina W.|||0000-0002-8933-3260, van der Flier, Wiesje M.|||0000-0001-8766-6224, Teunissen, Charlotte E.|||0000-0002-4061-0837, Campo Milán, Marta del|||0000-0003-2808-3699
Formato: artículo
Fecha de publicación:2023
País:España
Recursos:Universitat Autònoma de Barcelona
Repositorio:Dipòsit Digital de Documents de la UAB
Idioma:inglés
OAI Identifier:oai:ddd.uab.cat:291487
Acesso em linha:https://ddd.uab.cat/record/291487
https://dx.doi.org/urn:doi:10.1002/dad2.12456
Access Level:acceso abierto
Palavra-chave:Alzheimer's disease
Biomarkers
CSF
THOP1
Descrição
Resumo:Our previous antibody-based cerebrospinal fluid (CSF) proteomics study showed that Thimet oligopeptidase (THOP1), an amyloid beta (Aβ) neuropeptidase, was increased in mild cognitive impairment with amyloid pathology (MCI-Aβ+) and Alzheimer's disease (AD) dementia compared with controls and dementia with Lewy bodies (DLB), highlighting the potential of CSF THOP1 as an early specific biomarker for AD. We aimed to develop THOP1 immunoassays for large-scale analysis and validate our proteomics findings in two independent cohorts. We developed in-house CSF THOP1 immunoassays on automated Ella and Simoa platforms. The performance of the different assays were compared using Passing-Bablok regression analysis in a subset of CSF samples from the discovery cohort (n = 72). Clinical validation was performed in two independent cohorts (cohort 1: n = 200; cohort 2: n = 165) using the Ella platform. THOP1 concentrations moderately correlated between proteomics analysis and our novel assays (Rho.