Cerebrospinal Fluid Panel of Synaptic Proteins in Cerebral Amyloid Angiopathy and Alzheimer's Disease

Autor:	Emma van den Berg, Johanna Nilsson, Iris Kersten, Gunnar Brinkmalm, Anna M. de Kort, Catharina J.M. Klijn, Floris H.B.M. Schreuder, Lieke Jäkel, Johan Gobom, Erik Portelius, Henrik Zetterberg, Ann Brinkmalm, Kaj Blennow, H. Bea Kuiperij, Marcel M. Verbeek
Rok vydání:	2023
Předmět:	Psychiatry and Mental health Clinical Psychology All institutes and research themes of the Radboud University Medical Center General Neuroscience General Medicine Geriatrics and Gerontology Disorders of movement Donders Center for Medical Neuroscience [Radboudumc 3]
Zdroj:	Journal of Alzheimer's Disease, 92, 2, pp. 467-475 Journal of Alzheimer's Disease, 92, 467-475
ISSN:	1387-2877
Popis:	Contains fulltext : 291531.pdf (Publisher’s version ) (Open Access) BACKGROUND: Alzheimer's disease (AD) and cerebral amyloid angiopathy (CAA) share pathogenic pathways related to amyloid-β deposition. Whereas AD is known to affect synaptic function, such an association for CAA remains yet unknown. OBJECTIVE: We therefore aimed to investigate synaptic dysfunction in CAA. METHODS: Multiple reaction monitoring mass spectrometry was used to quantify cerebrospinal fluid (CSF) concentrations of 15 synaptic proteins in CAA and AD patients, and age- and sex-matched cognitively unimpaired controls. RESULTS: We included 25 patients with CAA, 49 patients with AD, and 25 controls. Only neuronal pentraxin-2 levels were decreased in the CSF of CAA patients compared with controls (p = 0.04). CSF concentrations of 12 other synaptic proteins were all increased in AD compared with CAA or controls (all p≤0.01) and were unchanged between CAA and controls. Synaptic protein concentrations in the subgroup of CAA patients positive for AD biomarkers (CAA/ATN+; n = 6) were similar to AD patients, while levels in CAA/ATN- (n = 19) were comparable with those in controls. A regression model including all synaptic proteins differentiated CAA from AD at high accuracy levels (area under the curve 0.987). CONCLUSION: In contrast to AD, synaptic CSF biomarkers were found to be largely unchanged in CAA. Moreover, concomitant AD pathology in CAA is associated with abnormal synaptic protein levels. Impaired synaptic function in AD was confirmed in this independent cohort. Our findings support an apparent differential involvement of synaptic dysfunction in CAA and AD and may reflect distinct pathological mechanisms.
Databáze:	OpenAIRE
Externí odkaz:	https://explore.openaire.eu/search/publication?articleId=doi_dedup___::7c0816f2bc81cc8e38d8e65824799abd https://doi.org/10.3233/JAD-220977 Zobrazit plný text záznamu