{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,30]],"date-time":"2026-08-30T23:16:06Z","timestamp":1788131766752,"version":"build-2803163510"},"reference-count":54,"publisher":"Oxford University Press (OUP)","issue":"2","license":[{"start":{"date-parts":[[2025,2,21]],"date-time":"2025-02-21T00:00:00Z","timestamp":1740096000000},"content-version":"vor","delay-in-days":51,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100004359","name":"Swedish Research Council","doi-asserted-by":"publisher","award":["#2020-02325"],"award-info":[{"award-number":["#2020-02325"]}],"id":[{"id":"10.13039\/501100004359","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100018713","name":"Center for Innovative Medicine","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100018713","id-type":"DOI","asserted-by":"publisher"}]},{"name":"Region Stockholm","award":["#FoUI-954431"],"award-info":[{"award-number":["#FoUI-954431"]}]},{"name":"Swedish state support for clinical research","award":["#ALFSTO-501484"],"award-info":[{"award-number":["#ALFSTO-501484"]}]},{"name":"Swedish state support for clinical research","award":["#ALFSTO-592522"],"award-info":[{"award-number":["#ALFSTO-592522"]}]},{"name":"European Union\u2019s Horizon 2020 research","award":["860197"],"award-info":[{"award-number":["860197"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2025,3,4]]},"abstract":"<jats:title>Abstract<\/jats:title>\n               <jats:p>Alzheimer\u2019s disease and related dementias have a multifactorial aetiology and heterogeneous biology. The current study aims to identify different biological signatures in a deeply phenotyped memory clinic patient population. In this cross-sectional study, we analysed 49 pre-specified proteins using a multiplex antibody-based suspension bead array in 278 CSF samples from the real-world research database and biobank at the Karolinska University Hospital Memory Clinic, Solna, Sweden. Patients with a clinical diagnosis of subjective cognitive decline (N = 151), mild cognitive impairment (N = 61), Alzheimer\u2019s disease (N = 47), or other diagnoses (N = 19; vascular dementias, alcohol-related dementia, unspecified dementias, or other amnesias) were included. Principal component analyses were performed, and resulting principal components (PCs) were tested for associations with clinical variables and Alzheimer\u2019s disease biomarkers (CSF biomarkers beta-amyloid 42, beta-amyloid 42\/40, phosphorylated tau 181, phosphorylated tau 181\/beta-amyloid 42). PC 1 (explaining 52% of the variance between patients) was associated with the clinical Alzheimer\u2019s disease CSF biomarkers beta-amyloid 42, phosphorylated tau 181, and total tau but not with Alzheimer\u2019s disease-related neurodegeneration imaging markers, cognitive performance, or clinical diagnosis. PC 2 (explaining 9% of the variance) displayed an inflammatory profile with high contributions of chitinase 3 like 1 (CHI3L1) and triggering receptor expressed on myeloid cells 2 (TREM2) and significant correlation to CSF free light chain kappa. In contrast to PC 1, PC 3 (explaining 5% of the variance) showed associations with all the clinical Alzheimer\u2019s disease CSF biomarkers, the imaging markers, cognitive impairment and clinical diagnosis. Serpin family A member 3 (SERPINA3), chitinase 1 (CHIT1), and neuronal pentraxin 2 (NPTX2) contributed most to PC 3. PC 4 (explaining 4% of the variance) exhibited an inflammatory profile distinct from PC 2, with the largest contributions from TREM2, leucine-rich alpha-2-glycoprotein 1 (LRG1) and complement C9. The component was associated with peripheral inflammation. We found that CSF protein profiles in a memory clinic cohort reflect molecular differences across diagnostic groups. Our results emphasize that real-world memory clinic patients can have different ongoing biological processes despite receiving the same diagnosis. In the future, this information could be utilized to identify patient endotypes and uncover precision biomarkers and novel therapeutic targets.<\/jats:p>","DOI":"10.1093\/braincomms\/fcaf078","type":"journal-article","created":{"date-parts":[[2025,2,21]],"date-time":"2025-02-21T18:28:41Z","timestamp":1740162521000},"source":"Crossref","is-referenced-by-count":3,"title":["Biological signatures in the Alzheimer\u2019s continuum discriminate between diagnosis-related and -unrelated associations to ATN categories"],"prefix":"10.1093","volume":"7","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-9918-9429","authenticated-orcid":false,"given":"Vilma","family":"Alanko","sequence":"first","affiliation":[{"name":"Division of Clinical Geriatrics, Department of Neurobiology, Care Sciences and Society, Karolinska Institutet , SE-171 77 Stockholm ,","place":["Sweden"]},{"name":"Division of Neurogeriatrics, Department of Neurobiology, Care Sciences and Society, Karolinska Institutet , SE-171 77 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,","place":["Finland"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0238-8646","authenticated-orcid":false,"given":"G\u00f6ran","family":"Hagman","sequence":"additional","affiliation":[{"name":"Division of Clinical Geriatrics, Department of Neurobiology, Care Sciences and Society, Karolinska Institutet , SE-171 77 Stockholm ,","place":["Sweden"]},{"name":"Theme Inflammation and Aging, Karolinska University Hospital , SE-171 76 Stockholm ,","place":["Sweden"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6499-1251","authenticated-orcid":false,"given":"Rosaleena","family":"Mohanty","sequence":"additional","affiliation":[{"name":"Division of Clinical Geriatrics, Department of Neurobiology, Care Sciences and Society, Karolinska Institutet , SE-171 77 Stockholm 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Clinical Geriatrics, Department of Neurobiology, Care Sciences and Society, Karolinska Institutet , SE-171 77 Stockholm ,","place":["Sweden"]},{"name":"Theme Inflammation and Aging, Karolinska University Hospital , SE-171 76 Stockholm ,","place":["Sweden"]},{"name":"Ageing Epidemiology Research Unit (AGE), School of Public Health, Imperial College London , London W12 OBZ ,","place":["United Kingdom"]},{"name":"Institute of Public Health and Clinical Nutrition, University of Eastern Finland , FI-70211 Kuopio ,","place":["Finland"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0056-1313","authenticated-orcid":false,"given":"Anna","family":"M\u00e5nberg","sequence":"additional","affiliation":[{"name":"Division of Affinity Proteomics, Department of Protein Science, KTH Royal Institute of Technology, SciLifeLab , SE-171 65 Stockholm 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