{"entity": "researcher", "timestamp": "2026-10-17T12:40:47.307Z", "family": "Pichet Binette", "given": "Alexa", "initials": "A", "orcid": "0000-0001-5218-3337", "affiliations": ["Clinical Memory Research Unit, Department of Clinical Sciences Malm\u00f6, Lund University, Lund, Sweden."], "links": {"self": {"href": "https://publications-affiliated.scilifelab.se/researcher/e8f0967b7b694bcf96e30a051a5bbe9a.json"}, "display": {"href": "https://publications-affiliated.scilifelab.se/researcher/e8f0967b7b694bcf96e30a051a5bbe9a"}}, "publications": [{"entity": "publication", "iuid": "41296afe1fb94394af66909057750160", "links": {"self": {"href": "https://publications-affiliated.scilifelab.se/publication/41296afe1fb94394af66909057750160.json"}, "display": {"href": "https://publications-affiliated.scilifelab.se/publication/41296afe1fb94394af66909057750160"}}, "title": "Hemispheric asymmetry of tau pathology is related to asymmetric amyloid deposition in Alzheimer's Disease.", "authors": [{"family": "Anij\u00e4rv", "given": "Toomas Erik", "initials": "TE", "orcid": "0000-0002-3650-4230", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/478837ec8fef4a8d9d4b39e088049614.json"}}, {"family": "Ossenkoppele", "given": "Rik", "initials": "R", "orcid": "0000-0003-1584-7477", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/9486d27ddd1b4b6485fa3ca10e0f3d82.json"}}, {"family": "Smith", "given": "Ruben", "initials": "R", "orcid": "0000-0001-7147-0112", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/9c69d9e76c884720afe20ce34b2c4d81.json"}}, {"family": "Pichet Binette", "given": "Alexa", "initials": "A", "orcid": "0000-0001-5218-3337", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/e8f0967b7b694bcf96e30a051a5bbe9a.json"}}, {"family": "Collij", "given": "Lyduine E", "initials": "LE", "orcid": "0000-0001-6263-1762", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/6612222d48fd4bdcaa7c091d38efcc2b.json"}}, {"family": "Behjat", "given": "Harry H", "initials": "HH", "orcid": "0000-0001-6729-6801", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/e5d1b40c4a8342eb841754961f1b3593.json"}}, {"family": "Rittmo", "given": "Jonathan", "initials": "J", "orcid": "0000-0001-5075-0166", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/f46afd59d3a44a18a35c560c3d2e37f3.json"}}, {"family": "Karlsson", "given": "Linda", "initials": "L", "orcid": "0000-0002-0630-772X", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/ead4d76d56ff439ba30689e7dfe3aae2.json"}}, {"family": "Ahmadi", "given": "Khazar", "initials": "K", "orcid": "0000-0002-3371-6211", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/5295cea5ead34b96a887d4055ccd659b.json"}}, {"family": "Strandberg", "given": "Olof", "initials": "O"}, {"family": "Alzheimer\u2019s Disease Neuroimaging Initiative", "given": "", "initials": ""}, {"family": "van Westen", "given": "Danielle", "initials": "D", "orcid": "0000-0001-8649-9874", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/38afd81dca574f4a9884a1ce97b78e50.json"}}, {"family": "Vogel", "given": "Jacob W", "initials": "JW", "orcid": "0000-0001-6394-9940", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/d2ad5af780c245da9b59a8c80a0b00ff.json"}}, {"family": "Stomrud", "given": "Erik", "initials": "E"}, {"family": "Palmqvist", "given": "Sebastian", "initials": "S", "orcid": "0000-0002-9267-1930", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/6fbd05e87cfb4057a1a7e41d9fb94aef.json"}}, {"family": "Mattsson-Carlgren", "given": "Niklas", "initials": "N", "orcid": "0000-0002-8885-7724", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/bb26ae59b2a04f369c5ebc2f2375195a.json"}}, {"family": "Spotorno", "given": "Nicola", "initials": "N", "orcid": "0000-0001-5404-8788", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/4851c8ec84264207bdf67c2fd04643da.json"}}, {"family": "Hansson", "given": "Oskar", "initials": "O", "orcid": "0000-0001-8467-7286", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/9292115deece4d9fafc8a02d4a430707.json"}}], "type": "journal article", "published": "2025-09-05", "journal": {"title": "Nat Commun", "issn": "2041-1723", "volume": "16", "issue": "1", "pages": "8232", "issn-l": "2041-1723"}, "abstract": "The distribution of tau pathology in Alzheimer's disease (AD) shows remarkable inter-individual heterogeneity, including hemispheric asymmetry. However, the factors driving this asymmetry remain poorly understood. Here we explore whether tau asymmetry is linked to i) reduced inter-hemispheric brain connectivity (potentially restricting tau spread), or ii) asymmetry in amyloid-beta (A\u03b2) distribution (indicating greater hemisphere-specific vulnerability to AD pathology). We include 452 participants from the Swedish BioFINDER-2 cohort with evidence of both A\u03b2 pathology (CSF A\u03b242/40 or neocortical A\u03b2-PET) and tau pathology (temporal tau-PET), categorising them as left asymmetric (n = 102), symmetric (n = 306), or right asymmetric (n = 44) based on temporal lobe tau-PET uptake distribution. We assess edge-wise inter-hemispheric functional (RSfMRI; n = 318) and structural connectivity (dMRI; n = 352) but find no association between tau asymmetry and connectivity. In contrast, we observe a strong association between tau and A\u03b2 laterality patterns based on PET uptake (n = 233; \u03b2 = 0.632, p < 0.001), which we replicate in three independent cohorts (n = 234; \u03b2 = 0.535, p < 0.001). In a longitudinal A\u03b2-positive sample, we show that baseline A\u03b2 asymmetry predicts progression of tau laterality over time (n = 289; \u03b2 = 0.025, p = 0.028). These findings suggest that tau asymmetry is not associated with a weaker inter-hemispheric connectivity but might reflect hemispheric differences in vulnerability to A\u03b2 pathology, underscoring the role of regional vulnerability in determining the distribution of AD pathology.", "doi": "10.1038/s41467-025-63564-2", "pmid": "40913038", "labels": [], "xrefs": [{"db": "pmc", "key": "PMC12413461"}, {"db": "pii", "key": "10.1038/s41467-025-63564-2"}], "notes": [], "created": "2026-08-21T11:50:12.353Z", "modified": "2026-10-01T08:24:55.333Z"}, {"entity": "publication", "iuid": "8e16e41a05b84805851dcab40b6d2049", "links": {"self": {"href": "https://publications-affiliated.scilifelab.se/publication/8e16e41a05b84805851dcab40b6d2049.json"}, "display": {"href": "https://publications-affiliated.scilifelab.se/publication/8e16e41a05b84805851dcab40b6d2049"}}, "title": "Proteomic signatures of the APOE \u03b54 and APOE \u03b52 genetic variants and Alzheimer's disease.", "authors": [{"family": "Lu", "given": "Lina", "initials": "L", "orcid": "0000-0001-9395-242X", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/2067c4e87b804659b8aee8603d3848e0.json"}}, {"family": "Binette", "given": "Alexa Pichet", "initials": "AP", "orcid": "0000-0001-5218-3337", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/e8f0967b7b694bcf96e30a051a5bbe9a.json"}}, {"family": "Hristovska", "given": "Ines", "initials": "I"}, {"family": "Janelidze", "given": "Shorena", "initials": "S"}, {"family": "Smets", "given": "Bart", "initials": "B"}, {"family": "Mayoral", "given": "Irene Cumplido", "initials": "IC", "orcid": "0000-0002-1967-7025", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/5486c50f78d9419484fb75d726dffb3e.json"}}, {"family": "Vasanthakumar", "given": "Aparna", "initials": "A"}, {"family": "Milkovich", "given": "Britney", "initials": "B"}, {"family": "Ossenkoppele", "given": "Rik", "initials": "R", "orcid": "0000-0003-1584-7477", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/9486d27ddd1b4b6485fa3ca10e0f3d82.json"}}, {"family": "Krish", "given": "Varsha", "initials": "V"}, {"family": "Imam", "given": "Farhad", "initials": "F"}, {"family": "Palmqvist", "given": "Sebastian", "initials": "S", "orcid": "0000-0002-9267-1930", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/6fbd05e87cfb4057a1a7e41d9fb94aef.json"}}, {"family": "Vogel", "given": "Jacob", "initials": "J"}, {"family": "Stomrud", "given": "Erik", "initials": "E", "orcid": "0000-0002-0841-5580", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/ac36a615800c40b98d64369cb029497c.json"}}, {"family": "Hansson", "given": "Oskar", "initials": "O", "orcid": "0000-0001-8467-7286", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/9292115deece4d9fafc8a02d4a430707.json"}}, {"family": "Mattsson-Carlgren", "given": "Niklas", "initials": "N", "orcid": "0000-0002-8885-7724", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/bb26ae59b2a04f369c5ebc2f2375195a.json"}}], "type": "journal article", "published": "2025-08-25", "journal": {"title": "medRxiv", "issn-l": null}, "abstract": "The \u03b54 and \u03b52 alleles of the Apolipoprotein E (APOE) gene confer opposite genetic risks for Alzheimer's disease (AD), but their underlying molecular mechanisms remain poorly characterized in humans. To resolve this, we systematically profiled APOE-associated proteomic alterations across five cohorts-including the Global Neurodegeneration Proteomics Consortium (GNPC), BioFINDER-2, the Alzheimer's Disease Neuroimaging Initiative (ADNI), the Parkinson's Progression Markers Initiative (PPMI), and UK Biobank (UKB)-using SomaLogic and OLINK platforms in plasma and cerebrospinal fluid (CSF) from over 10,000 individuals. Using GNPC (plasma SomaLogic, N=4,045), we mapped a comprehensive APOE-protein network and applied mediation modeling to classify genotype-related signals as upstream mediators, downstream consequences, or APOE-specific changes. We then leveraged CSF beta-amyloid (A\u03b2) biomarker data from BioFINDER-2 (plasma SomaLogic, N=1,421) to improve temporal resolution and isolate early, A\u03b2-independent proteomic programs. In the A\u03b2- individuals, APOE4 was linked to cell cycle and chromatin remodeling, while APOE2 was associated with mitochondrial regulation and DNA repair. Mediation analyses nominated proteins such as S100A13, TBCA, SPC25 for APOE4, and APOB, SNAP23 for APOE2 as candidate upstream effectors, supported by CSF validation (ADNI, SomaLogic, N=666), brain transcriptomic co-expression, and AD GWAS colocalization. Longitudinal CSF data from PPMI confirmed the temporal stability of several APOE-associated proteins. Cross-platform comparisons (UKB plasma OLINK, N=4,820, and BF2 CSF OLINK, N=1,475) revealed matrix- and assay-specific heterogeneity, underscoring challenges in reproducibility. Together, our results delineate allele-specific, temporally structured proteomic signatures that precede AD pathology, offering insight into APOE-driven molecular pathways and potential therapeutic targets for early intervention.", "doi": "10.1101/2025.08.04.25332945", "pmid": "40799961", "labels": [], "xrefs": [{"db": "pmc", "key": "PMC12340876"}, {"db": "pii", "key": "2025.08.04.25332945"}], "notes": [], "created": "2026-10-01T08:34:37.305Z", "modified": "2026-10-01T08:34:37.445Z"}, {"entity": "publication", "iuid": "5f981cbb10d5403baea20853de7d39ad", "links": {"self": {"href": "https://publications-affiliated.scilifelab.se/publication/5f981cbb10d5403baea20853de7d39ad.json"}, "display": {"href": "https://publications-affiliated.scilifelab.se/publication/5f981cbb10d5403baea20853de7d39ad"}}, "title": "Benchmarking the AI-based diagnostic potential of plasma proteomics for neurodegenerative disease in 17,170 people.", "authors": [{"family": "An", "given": "Lijun", "initials": "L", "orcid": "0000-0003-1030-4625", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/06744ec5a4ad4223b88038071e7b1dbf.json"}}, {"family": "Pichet-Binette", "given": "Alexa", "initials": "A", "orcid": "0000-0001-5218-3337", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/e8f0967b7b694bcf96e30a051a5bbe9a.json"}}, {"family": "Hristovska", "given": "Ines", "initials": "I"}, {"family": "Vilkaite", "given": "Gabriele", "initials": "G", "orcid": "0009-0009-6985-4307", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/fc705f5708ae447ea1ebd6a3a0bd73cf.json"}}, {"family": "Yu", "given": "Xiao", "initials": "X", "orcid": "0009-0006-6760-4134", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/49c14c0be1f2486bb835dd3090785268.json"}}, {"family": "Smets", "given": "Bart", "initials": "B"}, {"family": "Saloner", "given": "Rowan", "initials": "R", "orcid": "0000-0002-1351-6183", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/23de862940594622a28cb1e1c78b4447.json"}}, {"family": "Tasaki", "given": "Shinya", "initials": "S", "orcid": "0000-0003-3656-7394", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/741c7fb0f6044af6a9cae7b128972b10.json"}}, {"family": "Xu", "given": "Ying", "initials": "Y"}, {"family": "Krish", "given": "Varsha", "initials": "V"}, {"family": "Imam", "given": "Farhad", "initials": "F", "orcid": "0000-0003-2854-2568", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/a4b307d7379c43498446d995e26ef596.json"}}, {"family": "Janelidze", "given": "Shorena", "initials": "S", "orcid": "0000-0003-2869-8378", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/a3e2ab428bdc42838f5af521a4d8b862.json"}}, {"family": "van Westen", "given": "Danielle", "initials": "D", "orcid": "0000-0001-8649-9874", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/38afd81dca574f4a9884a1ce97b78e50.json"}}, {"family": "Global Neurodegeneration Proteomics Consortium (GNPC)", "given": "", "initials": ""}, {"family": "Stomrud", "given": "Erik", "initials": "E", "orcid": "0000-0002-0841-5580", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/ac36a615800c40b98d64369cb029497c.json"}}, {"family": "Whelan", "given": "Christopher D", "initials": "CD", "orcid": "0000-0003-0308-5583", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/172a710cb4974f168783a34e02eca6ee.json"}}, {"family": "Palmqvist", "given": "Sebastian", "initials": "S", "orcid": "0000-0002-9267-1930", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/6fbd05e87cfb4057a1a7e41d9fb94aef.json"}}, {"family": "Ossenkoppele", "given": "Rik", "initials": "R", "orcid": "0000-0003-1584-7477", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/9486d27ddd1b4b6485fa3ca10e0f3d82.json"}}, {"family": "Mattsson-Carlgren", "given": "Niklas", "initials": "N", "orcid": "0000-0002-8885-7724", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/bb26ae59b2a04f369c5ebc2f2375195a.json"}}, {"family": "Hansson", "given": "Oskar", "initials": "O", "orcid": "0000-0001-8467-7286", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/9292115deece4d9fafc8a02d4a430707.json"}}, {"family": "Vogel", "given": "Jacob W", "initials": "JW", "orcid": "0000-0001-6394-9940", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/d2ad5af780c245da9b59a8c80a0b00ff.json"}}], "type": "journal article", "published": "2025-07-01", "journal": {"title": "medRxiv", "issn-l": null}, "abstract": "Co-pathology is a common feature of neurodegenerative diseases that complicates diagnosis, treatment and clinical management. However, sensitive, specific and scalable biomarkers for in vivo pathological diagnosis are not available for most neurodegenerative neuropathologies. Here, we present ProtAIDe-Dx, a deep joint-learning model trained on 17,170 patients and controls that uses plasma proteomics to provide simultaneous probabilistic diagnosis across six conditions associated with dementia in aging. ProtAIDe-Dx achieves cross-validated balanced classification accuracy of 69%-96% and AUCs > 79% across all conditions. The model's diagnostic probabilities highlighted subgroups of patients with co-pathologies, and were associated with pathology-specific biomarkers in an external sample, even among cognitively unimpaired people. Model interpretation revealed a suite of protein networks marking shared and specific biological processes across diseases, and identified novel and previously described proteins discriminating each diagnosis. ProtAIDe-Dx significantly improved biomarker-based differential diagnosis in a memory clinic sample, pinpointing proteins leading to diagnostic decisions at an individual level. Together, this work highlights the promise of plasma proteomics to improve patient-level diagnostic work-up with a single blood draw.", "doi": "10.1101/2025.06.27.25330344", "pmid": "40630573", "labels": [], "xrefs": [{"db": "pmc", "key": "PMC12236936"}, {"db": "pii", "key": "2025.06.27.25330344"}], "notes": [], "created": "2026-08-20T11:06:20.965Z", "modified": "2026-09-23T14:28:43.092Z"}, {"entity": "publication", "iuid": "9d9906f7aee144eeab4a77c395e2c6ff", "links": {"self": {"href": "https://publications-affiliated.scilifelab.se/publication/9d9906f7aee144eeab4a77c395e2c6ff.json"}, "display": {"href": "https://publications-affiliated.scilifelab.se/publication/9d9906f7aee144eeab4a77c395e2c6ff"}}, "title": "Hemispheric Asymmetry of Tau Pathology is Related to Asymmetric Amyloid Deposition in Alzheimer\u2019s Disease", "authors": [{"family": "Anij\u00e4rv", "given": "T E", "initials": "TE", "orcid": "0000-0002-3650-4230", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/478837ec8fef4a8d9d4b39e088049614.json"}}, {"family": "Ossenkoppele", "given": "R", "initials": "R", "orcid": "0000-0003-1584-7477", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/9486d27ddd1b4b6485fa3ca10e0f3d82.json"}}, {"family": "Smith", "given": "R", "initials": "R", "orcid": "0000-0001-7147-0112", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/9c69d9e76c884720afe20ce34b2c4d81.json"}}, {"family": "Binette", "given": "A P", "initials": "AP", "orcid": "0000-0001-5218-3337", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/e8f0967b7b694bcf96e30a051a5bbe9a.json"}}, {"family": "Collij", "given": "L E", "initials": "LE", "orcid": "0000-0001-6263-1762", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/6612222d48fd4bdcaa7c091d38efcc2b.json"}}, {"family": "Behjat", "given": "H H", "initials": "HH", "orcid": "0000-0001-6729-6801", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/e5d1b40c4a8342eb841754961f1b3593.json"}}, {"family": "Rittmo", "given": "J", "initials": "J", "orcid": "0000-0001-5075-0166", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/f46afd59d3a44a18a35c560c3d2e37f3.json"}}, {"family": "Karlsson", "given": "L", "initials": "L", "orcid": "0000-0002-0630-772X", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/ead4d76d56ff439ba30689e7dfe3aae2.json"}}, {"family": "Ahmadi", "given": "K", "initials": "K", "orcid": "0000-0002-3371-6211", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/5295cea5ead34b96a887d4055ccd659b.json"}}, {"family": "Strandberg", "given": "O", "initials": "O"}, {"family": "van Westen", "given": "D", "initials": "D", "orcid": "0000-0001-8649-9874", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/38afd81dca574f4a9884a1ce97b78e50.json"}}, {"family": "Vogel", "given": "J W", "initials": "JW", "orcid": "0000-0001-6394-9940", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/d2ad5af780c245da9b59a8c80a0b00ff.json"}}, {"family": "Stomrud", "given": "E", "initials": "E", "orcid": "0000-0002-0841-5580", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/ac36a615800c40b98d64369cb029497c.json"}}, {"family": "Palmqvist", "given": "S", "initials": "S", "orcid": "0000-0002-9267-1930", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/6fbd05e87cfb4057a1a7e41d9fb94aef.json"}}, {"family": "Mattsson-Carlgren", "given": "N", "initials": "N", "orcid": "0000-0002-8885-7724", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/bb26ae59b2a04f369c5ebc2f2375195a.json"}}, {"family": "Spotorno", "given": "N", "initials": "N", "orcid": "0000-0001-5404-8788", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/4851c8ec84264207bdf67c2fd04643da.json"}}, {"family": "Hansson", "given": "O", "initials": "O", "orcid": "0000-0001-8467-7286", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/9292115deece4d9fafc8a02d4a430707.json"}}], "type": "posted-content", "published": "2025-04-19", "journal": {"issn-l": null}, "abstract": null, "doi": "10.1101/2025.04.15.648728", "pmid": null, "labels": [], "xrefs": [], "notes": [], "created": "2026-10-01T08:32:24.180Z", "modified": "2026-10-01T08:32:24.279Z"}, {"entity": "publication", "iuid": "1070918999b3451da1cb45b9ab4e789c", "links": {"self": {"href": "https://publications-affiliated.scilifelab.se/publication/1070918999b3451da1cb45b9ab4e789c.json"}, "display": {"href": "https://publications-affiliated.scilifelab.se/publication/1070918999b3451da1cb45b9ab4e789c"}}, "title": "Proteomic changes in Alzheimer's disease associated with progressive A\u03b2 plaque and tau tangle pathologies.", "authors": [{"family": "Pichet Binette", "given": "Alexa", "initials": "A", "orcid": "0000-0001-5218-3337", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/e8f0967b7b694bcf96e30a051a5bbe9a.json"}}, {"family": "Gaiteri", "given": "Chris", "initials": "C"}, {"family": "Wennstr\u00f6m", "given": "Malin", "initials": "M"}, {"family": "Kumar", "given": "Atul", "initials": "A"}, {"family": "Hristovska", "given": "Ines", "initials": "I"}, {"family": "Spotorno", "given": "Nicola", "initials": "N"}, {"family": "Salvad\u00f3", "given": "Gemma", "initials": "G", "orcid": "0000-0002-5210-9230", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/c3b7599000404d618d84b389ba47f19a.json"}}, {"family": "Strandberg", "given": "Olof", "initials": "O"}, {"family": "Mathys", "given": "Hansruedi", "initials": "H", "orcid": "0000-0003-0186-2115", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/38b5ab2013214cc7845021e2460b3433.json"}}, {"family": "Tsai", "given": "Li-Huei", "initials": "LH", "orcid": "0000-0003-1262-0592", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/fd0b5f35b80a4fb580612e498d06c75b.json"}}, {"family": "Palmqvist", "given": "Sebastian", "initials": "S", "orcid": "0000-0002-9267-1930", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/6fbd05e87cfb4057a1a7e41d9fb94aef.json"}}, {"family": "Mattsson-Carlgren", "given": "Niklas", "initials": "N"}, {"family": "Janelidze", "given": "Shorena", "initials": "S"}, {"family": "Stomrud", "given": "Erik", "initials": "E"}, {"family": "Vogel", "given": "Jacob W", "initials": "JW"}, {"family": "Hansson", "given": "Oskar", "initials": "O", "orcid": "0000-0001-8467-7286", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/9292115deece4d9fafc8a02d4a430707.json"}}], "type": "journal article", "published": "2024-10-00", "journal": {"title": "Nat. Neurosci.", "issn": "1546-1726", "volume": "27", "issue": "10", "pages": "1880-1891", "issn-l": "1097-6256"}, "abstract": "Proteomics can shed light on the dynamic and multifaceted alterations in neurodegenerative disorders like Alzheimer's disease (AD). Combining radioligands measuring \u03b2-amyloid (A\u03b2) plaques and tau tangles with cerebrospinal fluid proteomics, we uncover molecular events mirroring different stages of AD pathology in living humans. We found 127 differentially abundant proteins (DAPs) across the AD spectrum. The strongest A\u03b2-related proteins were mainly expressed in glial cells and included SMOC1 and ITGAM. A dozen proteins linked to ATP metabolism and preferentially expressed in neurons were independently associated with tau tangle load and tau accumulation. Only 20% of the DAPs were also altered in other neurodegenerative diseases, underscoring AD's distinct proteome. Two co-expression modules related, respectively, to protein metabolism and microglial immune response encompassed most DAPs, with opposing, staggered trajectories along the AD continuum. We unveil protein signatures associated with A\u03b2 and tau proteinopathy in vivo, offering insights into complex neural responses and potential biomarkers and therapeutics targeting different disease stages.", "doi": "10.1038/s41593-024-01737-w", "pmid": "39187705", "labels": {"Jacob W Vogel": null, "DDLS Fellow": null}, "xrefs": [{"db": "pmc", "key": "PMC11452344"}, {"db": "pii", "key": "10.1038/s41593-024-01737-w"}], "notes": [], "created": "2025-03-19T11:17:10.669Z", "modified": "2025-03-19T11:19:18.053Z"}, {"entity": "publication", "iuid": "119372bc0180412e8486e4b2fa20522b", "links": {"self": {"href": "https://publications-affiliated.scilifelab.se/publication/119372bc0180412e8486e4b2fa20522b.json"}, "display": {"href": "https://publications-affiliated.scilifelab.se/publication/119372bc0180412e8486e4b2fa20522b"}}, "title": "Disease staging of Alzheimer's disease using a CSF-based biomarker model.", "authors": [{"family": "Salvad\u00f3", "given": "Gemma", "initials": "G", "orcid": "0000-0002-5210-9230", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/c3b7599000404d618d84b389ba47f19a.json"}}, {"family": "Horie", "given": "Kanta", "initials": "K", "orcid": "0000-0001-7736-2614", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/a39cbb87fbd940fe830fef9c5d1ad9d5.json"}}, {"family": "Barth\u00e9lemy", "given": "Nicolas R", "initials": "NR", "orcid": "0000-0003-4937-2860", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/2e2661ed001644c68ff9513b271bbe7b.json"}}, {"family": "Vogel", "given": "Jacob W", "initials": "JW", "orcid": "0000-0001-6394-9940", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/d2ad5af780c245da9b59a8c80a0b00ff.json"}}, {"family": "Pichet Binette", "given": "Alexa", "initials": "A", "orcid": "0000-0001-5218-3337", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/e8f0967b7b694bcf96e30a051a5bbe9a.json"}}, {"family": "Chen", "given": "Charles D", "initials": "CD", "orcid": "0000-0001-6698-1268", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/aff8a335b4394feb8add3b1feb5f2812.json"}}, {"family": "Aschenbrenner", "given": "Andrew J", "initials": "AJ"}, {"family": "Gordon", "given": "Brian A", "initials": "BA", "orcid": "0000-0003-2109-2955", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/5d260cb618f240bc839bdb8b607c5418.json"}}, {"family": "Benzinger", "given": "Tammie L S", "initials": "TLS", "orcid": "0000-0002-8114-0552", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/edc53d42fddc4d3db2b7abbbac246223.json"}}, {"family": "Holtzman", "given": "David M", "initials": "DM"}, {"family": "Morris", "given": "John C", "initials": "JC"}, {"family": "Palmqvist", "given": "Sebastian", "initials": "S", "orcid": "0000-0002-9267-1930", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/6fbd05e87cfb4057a1a7e41d9fb94aef.json"}}, {"family": "Stomrud", "given": "Erik", "initials": "E"}, {"family": "Janelidze", "given": "Shorena", "initials": "S", "orcid": "0000-0003-2869-8378", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/a3e2ab428bdc42838f5af521a4d8b862.json"}}, {"family": "Ossenkoppele", "given": "Rik", "initials": "R"}, {"family": "Schindler", "given": "Suzanne E", "initials": "SE"}, {"family": "Bateman", "given": "Randall J", "initials": "RJ", "orcid": "0000-0002-7729-1702", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/0dd2354822ab40feacbdd2168370d582.json"}}, {"family": "Hansson", "given": "Oskar", "initials": "O", "orcid": "0000-0001-8467-7286", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/9292115deece4d9fafc8a02d4a430707.json"}}], "type": "journal article", "published": "2024-05-00", "journal": {"title": "Nat Aging", "issn": "2662-8465", "volume": "4", "issue": "5", "pages": "694-708", "issn-l": null}, "abstract": "Biological staging of individuals with Alzheimer's disease (AD) may improve diagnostic and prognostic workup of dementia in clinical practice and the design of clinical trials. In this study, we used the Subtype and Stage Inference (SuStaIn) algorithm to establish a robust biological staging model for AD using cerebrospinal fluid (CSF) biomarkers. Our analysis involved 426 participants from BioFINDER-2 and was validated in 222 participants from the Knight Alzheimer Disease Research Center cohort. SuStaIn identified a singular biomarker sequence and revealed that five CSF biomarkers effectively constituted a reliable staging model (ordered: A\u03b242/40, pT217/T217, pT205/T205, MTBR-tau243 and non-phosphorylated mid-region tau). The CSF stages (0-5) demonstrated a correlation with increased abnormalities in other AD-related biomarkers, such as A\u03b2-PET and tau-PET, and aligned with longitudinal biomarker changes reflective of AD progression. Higher CSF stages at baseline were associated with an elevated hazard ratio of clinical decline. This study highlights a common molecular pathway underlying AD pathophysiology across all patients, suggesting that a single CSF collection can accurately indicate the presence of AD pathologies and characterize the stage of disease progression. The proposed staging model has implications for enhancing diagnostic and prognostic assessments in both clinical practice and the design of clinical trials.", "doi": "10.1038/s43587-024-00599-y", "pmid": "38514824", "labels": {"Jacob W Vogel": null, "DDLS Fellow": null}, "xrefs": [{"db": "mid", "key": "NIHMS1986363"}, {"db": "pmc", "key": "PMC11108782"}, {"db": "pii", "key": "10.1038/s43587-024-00599-y"}], "notes": [], "created": "2025-03-19T11:17:00.164Z", "modified": "2025-03-19T11:19:05.978Z"}]}