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Phenotypic Displays of Cholinergic Enzymes Associate With Markers of Inflammation, Neurofibrillary Tangles, and Neurodegeneration in Pre- and Early Symptomatic Dementia Subjects

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dc.contributor Landspitali - The National University Hospital of Iceland
dc.contributor.author Teitsdottir, Unnur D.
dc.contributor.author Darreh-Shori, Taher
dc.contributor.author Lund, Sigrun H.
dc.contributor.author Jonsdottir, Maria K.
dc.contributor.author Snaedal, Jon
dc.contributor.author Petersen, Petur H.
dc.date.accessioned 2022-09-20T01:02:41Z
dc.date.available 2022-09-20T01:02:41Z
dc.date.issued 2022-05-26
dc.identifier.citation Teitsdottir , U D , Darreh-Shori , T , Lund , S H , Jonsdottir , M K , Snaedal , J & Petersen , P H 2022 , ' Phenotypic Displays of Cholinergic Enzymes Associate With Markers of Inflammation, Neurofibrillary Tangles, and Neurodegeneration in Pre- and Early Symptomatic Dementia Subjects ' , Frontiers in Aging Neuroscience , vol. 14 , 876019 , pp. 876019 . https://doi.org/10.3389/fnagi.2022.876019
dc.identifier.issn 1663-4365
dc.identifier.other PURE: 59618455
dc.identifier.other PURE UUID: a8a7df88-f01d-4319-b8b9-02f48b0fb2cf
dc.identifier.other Scopus: 85132102062
dc.identifier.uri https://hdl.handle.net/20.500.11815/3471
dc.description Funding Information: This study was supported by the St. Josef’s Hospital Fund, Reykjavik, Iceland, the Landspitali University Hospital Research Fund, and the Icelandic Research Fund of the Icelandic Centre for Research (163172-051). Publisher Copyright: Copyright © 2022 Teitsdottir, Darreh-Shori, Lund, Jonsdottir, Snaedal and Petersen. Copyright © 2022 Teitsdottir, Darreh-Shori, Lund, Jonsdottir, Snaedal and Petersen.
dc.description.abstract Background: Cholinergic drugs are the most commonly used drugs for the treatment of Alzheimer's disease (AD). Therefore, a better understanding of the cholinergic system and its relation to both AD-related biomarkers and cognitive functions is of high importance. Objectives: To evaluate the relationships of cerebrospinal fluid (CSF) cholinergic enzymes with markers of amyloidosis, neurodegeneration, neurofibrillary tangles, inflammation and performance on verbal episodic memory in a memory clinic cohort. Methods: In this cross-sectional study, 46 cholinergic drug-free subjects (median age = 71, 54% female, median MMSE = 28) were recruited from an Icelandic memory clinic cohort targeting early stages of cognitive impairment. Enzyme activity of acetylcholinesterase (AChE) and butyrylcholinesterase (BuChE) was measured in CSF as well as levels of amyloid-β 1-42 (Aβ 42), phosphorylated tau (P-tau), total-tau (T-tau), neurofilament light (NFL), YKL-40, S100 calcium-binding protein B (S100B), and glial fibrillary acidic protein (GFAP). Verbal episodic memory was assessed with the Rey Auditory Verbal Learning (RAVLT) and Story tests. Results: No significant relationships were found between CSF Aβ 42 levels and AChE or BuChE activity ( p > 0.05). In contrast, T-tau ( r = 0.46, p = 0.001) and P-tau ( r = 0.45, p = 0.002) levels correlated significantly with AChE activity. Although neurodegeneration markers T-tau and NFL did correlate with each other ( r = 0.59, p < 0.001), NFL did not correlate with AChE ( r = 0.25, p = 0.09) or BuChE ( r = 0.27, p = 0.06). Inflammation markers S100B and YKL-40 both correlated significantly with AChE (S100B: r = 0.43, p = 0.003; YKL-40: r = 0.32, p = 0.03) and BuChE (S100B: r = 0.47, p < 0.001; YKL-40: r = 0.38, p = 0.009) activity. A weak correlation was detected between AChE activity and the composite score reflecting verbal episodic memory ( r = -0.34, p = 0.02). LASSO regression analyses with a stability approach were performed for the selection of a set of measures best predicting cholinergic activity and verbal episodic memory score. S100B was the predictor with the highest model selection frequency for both AChE (68%) and BuChE (73%) activity. Age (91%) was the most reliable predictor for verbal episodic memory, with selection frequency of both cholinergic enzymes below 10%. Conclusions: Results indicate a relationship between higher activity of the ACh-degrading cholinergic enzymes with increased neurodegeneration, neurofibrillary tangles and inflammation in the stages of pre- and early symptomatic dementia, independent of CSF Aβ 42 levels.
dc.format.extent 876019
dc.language.iso en
dc.relation.ispartofseries Frontiers in Aging Neuroscience; 14()
dc.rights info:eu-repo/semantics/openAccess
dc.subject Öldrunarlæknisfræði
dc.subject Sálfræði
dc.subject acetylcholinesterase
dc.subject Alzheimer’s disease
dc.subject biomarkers
dc.subject butyrylcholinesterase
dc.subject cerebrospinal fluid
dc.subject cholinergic system
dc.subject inflammation
dc.subject neurodegenaration
dc.subject Aging
dc.subject Cognitive Neuroscience
dc.title Phenotypic Displays of Cholinergic Enzymes Associate With Markers of Inflammation, Neurofibrillary Tangles, and Neurodegeneration in Pre- and Early Symptomatic Dementia Subjects
dc.type /dk/atira/pure/researchoutput/researchoutputtypes/contributiontojournal/article
dc.description.version Peer reviewed
dc.identifier.pmid 35693340
dc.identifier.doi https://doi.org/10.3389/fnagi.2022.876019
dc.relation.url http://www.scopus.com/inward/record.url?scp=85132102062&partnerID=8YFLogxK
dc.contributor.department Faculty of Medicine
dc.contributor.department Department of Psychology
dc.contributor.department Mental Health Services
dc.contributor.department Geriatric and Rehabilitation Services


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