Synaptic protein CSF levels relate to memory scores in individuals without dementia.

Autor:	Wesenhagen KEJ; Alzheimer Center Amsterdam, Vrije Universiteit Amsterdam, Amsterdam UMC., de Leeuw DM; Alzheimer Center Amsterdam, Vrije Universiteit Amsterdam, Amsterdam UMC., Tomassen J; Alzheimer Center Amsterdam, Vrije Universiteit Amsterdam, Amsterdam UMC., Gobom J; Sahlgrenska University Hospital., Bos I; Alzheimer Center Amsterdam, Vrije Universiteit Amsterdam, Amsterdam UMC., Vos SJB; Alzheimer Center Limburg, Maastricht University., Martinez-Lage P; CITA-Alzheimer Foundation., Tainta M; CITA-Alzheimer Foundation., Popp J; University Hospital of Lausanne., Peyratout G; University Hospital of Lausanne., Tsolaki M; AHEPA University Hospital, Aristotle University of Thessaloniki., Vandenberghe R; University Hospitals Leuven., Freund-Levi Y; Karolinska Institutet., Verhey F; Alzheimer Center Limburg, Maastricht University., Lovestone S; University of Oxford., Streffer J; University of Antwerp., Dobricic V; University of Lübeck., Blennow K; University of Gothenburg., Scheltens P; Alzheimer Center Amsterdam, Vrije Universiteit Amsterdam, Amsterdam UMC., Smit AB; VU University Amsterdam., Bertram L; University of Lübeck., Teunissen CE; Amsterdam Neuroscience, Amsterdam UMC, Vrije Universiteit., Zetterberg H; Sahlgrenska University Hospital., Tijms BM; Alzheimer Center Amsterdam, Vrije Universiteit Amsterdam, Amsterdam UMC.
Jazyk:	angličtina
Zdroj:	Research square [Res Sq] 2024 Jul 23. Date of Electronic Publication: 2024 Jul 23.
DOI:	10.21203/rs.3.rs-4607202/v1
Abstrakt:	Introduction: We investigated how cerebrospinal fluid levels of synaptic proteins associate with memory function in normal cognition (CN) and mild cognitive impairment (MCI), and investigated the effect of amyloid positivity on these associations. Methods: We included 242 CN (105(43%) abnormal amyloid), and 278 MCI individuals (183(66%) abnormal amyloid) from EMIF-AD MBD and ADNI. For 181 (EMIF-AD MBD) and 36 (ADNI) proteins with a synaptic annotation in SynGO, associations with word learning recall were analysed with linear models. Results: Subsets of synaptic proteins showed lower levels with worse recall in preclinical AD (EMIF-AD MBD: 7, ADNI: 5 proteins, none overlapping), prodromal AD (EMIF-AD MBD only, 27 proteins) and non-AD MCI (EMIF-AD MBD: 1, ADNI: 7 proteins). The majority of these associations were specific to these groups. Discussion: Synaptic disturbance-related memory impairment occurred very early in AD, indicating it may be relevant to develop therapies targeting the synapse early in the disease. Competing Interests: Declarations Competing Interests KB has served as a consultant, at advisory boards, or at data monitoring committees for Abcam, Axon, BioArctic, Biogen, JOMDD/Shimadzu. Julius Clinical, Lilly, MagQu, Novartis, Pharmatrophix, Prothena, Roche Diagnostics, and Siemens Healthineers, and is a co-founder of Brain Biomarker Solutions in Gothenburg AB (BBS), which is a part of the GU Ventures Incubator Program, outside the work presented in this paper. HZ has served at scientific advisory boards and/or as a consultant for Abbvie, Alector, Annexon, Artery Therapeutics, AZTherapies, CogRx, Denali, Eisai, Nervgen, Pinteon Therapeutics, Red Abbey Labs, Passage Bio, Roche, Samumed, Siemens Healthineers, Triplet Therapeutics, and Wave, has given lectures in symposia sponsored by Cellectricon, Fujirebio, Alzecure, Biogen, and Roche, and is a co-founder of Brain Biomarker Solutions in Gothenburg AB (BBS), which is a part of the GU Ventures Incubator Program. PS has acquired grants for the institution from GE Healthcare and Piramal and received consultancy/speaker fees paid to the institution from Novartis, Probiodrug, Biogen, Roche, and EIP Pharma, LLC in the past 2 years. CT received grants from the European Commission, the Dutch Research Council (ZonMW), Association of Frontotemporal Dementia/Alzheimer’s Drug Discovery Foundation, The Weston Brain Institute, Alzheimer Netherlands. Prof. dr. Teunissen has functioned in advisory boards of Roche, received non-financial support in the form of research consumables from ADxNeurosciences and Euroimmun, performed contract research or received grants from Probiodrug, Biogen, Esai, Toyama, Janssen Prevention Center, Boehringer, AxonNeurosciences, EIP farma, PeopleBio, Roche. The other authors report no conflict of interest.
Databáze:	MEDLINE
Externí odkaz:	Zobrazit plný text záznamu