{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,5]],"date-time":"2026-10-05T15:04:41Z","timestamp":1791212681088,"version":"4.1.0"},"reference-count":68,"publisher":"MDPI AG","issue":"9","license":[{"start":{"date-parts":[[2023,5,1]],"date-time":"2023-05-01T00:00:00Z","timestamp":1682899200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/100008982","name":"Qatar National Research Fund","doi-asserted-by":"publisher","award":["NPRP12S-0213-190080"],"award-info":[{"award-number":["NPRP12S-0213-190080"]}],"id":[{"id":"10.13039\/100008982","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100008982","name":"Qatar National Research Fund","doi-asserted-by":"publisher","award":["IDRP-2018-002"],"award-info":[{"award-number":["IDRP-2018-002"]}],"id":[{"id":"10.13039\/100008982","id-type":"DOI","asserted-by":"publisher"}]},{"name":"QBRI Interdisciplinary Research Program","award":["NPRP12S-0213-190080"],"award-info":[{"award-number":["NPRP12S-0213-190080"]}]},{"name":"QBRI Interdisciplinary Research Program","award":["IDRP-2018-002"],"award-info":[{"award-number":["IDRP-2018-002"]}]},{"name":"College of Health and Life Sciences, Hamad Bin Khalifa University, Qatar Foundation","award":["NPRP12S-0213-190080"],"award-info":[{"award-number":["NPRP12S-0213-190080"]}]},{"name":"College of Health and Life Sciences, Hamad Bin Khalifa University, Qatar Foundation","award":["IDRP-2018-002"],"award-info":[{"award-number":["IDRP-2018-002"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>Dementia is a progressive and debilitating neurological disease that affects millions of people worldwide. Identifying the minimally invasive biomarkers associated with dementia that could provide insights into the disease pathogenesis, improve early diagnosis, and facilitate the development of effective treatments is pressing. Proteomic studies have emerged as a promising approach for identifying the protein biomarkers associated with dementia. This pilot study aimed to investigate the plasma proteome profile and identify a panel of various protein biomarkers for dementia. We used a high-throughput proximity extension immunoassay to quantify 1090 proteins in 122 participants (22 with dementia, 64 with mild cognitive impairment (MCI), and 36 controls with normal cognitive function). Limma-based differential expression analysis reported the dysregulation of 61 proteins in the plasma of those with dementia compared with controls, and machine learning algorithms identified 17 stable diagnostic biomarkers that differentiated individuals with AUC = 0.98 \u00b1 0.02. There was also the dysregulation of 153 plasma proteins in individuals with dementia compared with those with MCI, and machine learning algorithms identified 8 biomarkers that classified dementia from MCI with an AUC of 0.87 \u00b1 0.07. Moreover, multiple proteins selected in both diagnostic panels such as NEFL, IL17D, WNT9A, and PGF were negatively correlated with cognitive performance, with a correlation coefficient (r2) \u2264 \u22120.47. Gene Ontology (GO) and pathway analysis of dementia-associated proteins implicated immune response, vascular injury, and extracellular matrix organization pathways in dementia pathogenesis. In conclusion, the combination of high-throughput proteomics and machine learning enabled us to identify a blood-based protein signature capable of potentially differentiating dementia from MCI and cognitively normal controls. Further research is required to validate these biomarkers and investigate the potential underlying mechanisms for the development of dementia.<\/jats:p>","DOI":"10.3390\/ijms24098117","type":"journal-article","created":{"date-parts":[[2023,5,1]],"date-time":"2023-05-01T13:54:46Z","timestamp":1682949286000},"page":"8117","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":35,"title":["Blood-Based Proteomic Profiling Identifies Potential Biomarker Candidates and Pathogenic Pathways in Dementia"],"prefix":"10.3390","volume":"24","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-8410-2324","authenticated-orcid":false,"given":"Hanan","family":"Ehtewish","sequence":"first","affiliation":[{"name":"College of Health and Life Sciences (CHLS), Hamad Bin Khalifa University (HBKU), Qatar Foundation (QF), Doha P.O. Box 34110, Qatar"},{"name":"Neurological Disorders Research Center, Qatar Biomedical Research Institute (QBRI), Hamad Bin Khalifa University (HBKU), Qatar Foundation (QF), Doha P.O. Box 34110, Qatar"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8974-1101","authenticated-orcid":false,"given":"Areej","family":"Mesleh","sequence":"additional","affiliation":[{"name":"College of Health and Life Sciences (CHLS), Hamad Bin Khalifa University (HBKU), Qatar Foundation (QF), Doha P.O. Box 34110, Qatar"},{"name":"Neurological Disorders Research Center, Qatar Biomedical Research Institute (QBRI), Hamad Bin Khalifa University (HBKU), Qatar Foundation (QF), Doha P.O. Box 34110, Qatar"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Georgios","family":"Ponirakis","sequence":"additional","affiliation":[{"name":"Department of Medicine, Weill Cornell Medicine-Qatar, Qatar Foundation (QF), Doha P.O. Box 24144, Qatar"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3697-3635","authenticated-orcid":false,"given":"Alberto","family":"De la Fuente","sequence":"additional","affiliation":[{"name":"Diabetes Research Center, Qatar Biomedical Research Institute (QBRI), Hamad Bin Khalifa University (HBKU), Qatar Foundation (QF), Doha P.O. Box 34110, Qatar"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Aijaz","family":"Parray","sequence":"additional","affiliation":[{"name":"The Neuroscience Institute, Academic Health System, Hamad Medical Corporation (HMC), Doha P.O. Box 3050, Qatar"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ilham","family":"Bensmail","sequence":"additional","affiliation":[{"name":"Proteomics Core Facility, Qatar Biomedical Research Institute (QBRI), Hamad Bin Khalifa University (HBKU), Qatar Foundation (QF), Doha P.O. Box 34110, Qatar"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Houari","family":"Abdesselem","sequence":"additional","affiliation":[{"name":"Proteomics Core Facility, Qatar Biomedical Research Institute (QBRI), Hamad Bin Khalifa University (HBKU), Qatar Foundation (QF), Doha P.O. Box 34110, Qatar"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marwan","family":"Ramadan","sequence":"additional","affiliation":[{"name":"Geriatric and Memory Clinic, Rumailah Hospital, Hamad Medical Corporation (HMC), Doha P.O. Box 3050, Qatar"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shafi","family":"Khan","sequence":"additional","affiliation":[{"name":"Geriatric and Memory Clinic, Rumailah Hospital, Hamad Medical Corporation (HMC), Doha P.O. Box 3050, Qatar"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mani","family":"Chandran","sequence":"additional","affiliation":[{"name":"Geriatric and Memory Clinic, Rumailah Hospital, Hamad Medical Corporation (HMC), Doha P.O. Box 3050, Qatar"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2816-5563","authenticated-orcid":false,"given":"Raheem","family":"Ayadathil","sequence":"additional","affiliation":[{"name":"The Neuroscience Institute, Academic Health System, Hamad Medical Corporation (HMC), Doha P.O. Box 3050, Qatar"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2147-9626","authenticated-orcid":false,"given":"Ahmed","family":"Elsotouhy","sequence":"additional","affiliation":[{"name":"The Neuroscience Institute, Academic Health System, Hamad Medical Corporation (HMC), Doha P.O. Box 3050, Qatar"},{"name":"Department of Clinical Radiology, Weill Cornell Medicine-Qatar, Qatar Foundation, Doha P.O. Box 24144, Qatar"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ahmed","family":"Own","sequence":"additional","affiliation":[{"name":"The Neuroscience Institute, Academic Health System, Hamad Medical Corporation (HMC), Doha P.O. Box 3050, Qatar"},{"name":"Neuroradiology Department, Hamad General Hospital, Hamad Medical Corporation, Doha P.O. Box 3050, Qatar"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hanadi","family":"Al Hamad","sequence":"additional","affiliation":[{"name":"Geriatric and Memory Clinic, Rumailah Hospital, Hamad Medical Corporation (HMC), Doha P.O. 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Box 34110, Qatar"},{"name":"Translational Cancer and Immunity Center, Qatar Biomedical Research Institute (QBRI), Hamad Bin Khalifa University (HBKU), Qatar Foundation (QF), Doha P.O. Box 34110, Qatar"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1546-1091","authenticated-orcid":false,"given":"Nehad M.","family":"Alajez","sequence":"additional","affiliation":[{"name":"College of Health and Life Sciences (CHLS), Hamad Bin Khalifa University (HBKU), Qatar Foundation (QF), Doha P.O. Box 34110, Qatar"},{"name":"Translational Cancer and Immunity Center, Qatar Biomedical Research Institute (QBRI), Hamad Bin Khalifa University (HBKU), Qatar Foundation (QF), Doha P.O. 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Box 34110, Qatar"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5060-916X","authenticated-orcid":false,"given":"Abdelilah","family":"Arredouani","sequence":"additional","affiliation":[{"name":"College of Health and Life Sciences (CHLS), Hamad Bin Khalifa University (HBKU), Qatar Foundation (QF), Doha P.O. Box 34110, Qatar"},{"name":"Diabetes Research Center, Qatar Biomedical Research Institute (QBRI), Hamad Bin Khalifa University (HBKU), Qatar Foundation (QF), Doha P.O. Box 34110, Qatar"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7188-8903","authenticated-orcid":false,"given":"Rayaz A.","family":"Malik","sequence":"additional","affiliation":[{"name":"Department of Medicine, Weill Cornell Medicine-Qatar, Qatar Foundation (QF), Doha P.O. 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Box 34110, Qatar"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2023,5,1]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"1778","DOI":"10.1212\/WNL.0b013e31828726f5","article-title":"Alzheimer Disease in the United States (2010\u20132050) Estimated Using the 2010 Census","volume":"80","author":"Hebert","year":"2013","journal-title":"Neurology"},{"key":"ref_2","doi-asserted-by":"crossref","unstructured":"Alzheimer\u2019s Association (2018). 2018 Alzheimer\u2019s Disease Facts and Figures. Alzheimer\u2019s Dement., 14, 367\u2013429.","DOI":"10.1016\/j.jalz.2018.02.001"},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"203","DOI":"10.1097\/00002093-200210000-00001","article-title":"Relative Frequencies of Alzheimer Disease, Lewy Body, Vascular and Frontotemporal Dementia, and Hippocampal Sclerosis in the State of Florida Brain Bank","volume":"16","author":"Barker","year":"2002","journal-title":"Alzheimer Dis. Assoc. Disord."},{"key":"ref_4","unstructured":"Prince, M.J., Wimo, A., Guerchet, M.M., Ali, G.C., Wu, Y.T., and Prina, M. (2015). World Alzheimer Report 2015: The Global Impact of Dementia, Alzheimer\u2019s Disease International."},{"key":"ref_5","unstructured":"United Nations Department of Economic and Social Affairs Population Division (2019). World Population Ageing 2019, United Nations Department of Economic and Social Affairs Population Division."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"423","DOI":"10.1111\/j.1745-7599.2008.00342.x","article-title":"Caregiver Burden among Dementia Patient Caregivers: A Review of the Literature","volume":"20","author":"Etters","year":"2008","journal-title":"J. Am. Acad. Nurse Pract."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"614","DOI":"10.1016\/S1474-4422(14)70090-0","article-title":"Advancing Research Diagnostic Criteria for Alzheimer\u2019s Disease: The IWG-2 Criteria Position Paper Advancing Research Diagnostic Criteria for Alzheimer\u2019s Disease: The IWG-2 Criteria","volume":"13","author":"Dubois","year":"2014","journal-title":"Lancet Neurol."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"535","DOI":"10.1016\/j.jalz.2018.02.018","article-title":"NIA-AA Research Framework: Toward a Biological Definition of Alzheimer\u2019s Disease","volume":"14","author":"Jack","year":"2018","journal-title":"Alzheimer\u2019s Dement."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"214","DOI":"10.1111\/joim.12190","article-title":"Mild Cognitive Impairment: A Concept in Evolution","volume":"275","author":"Petersen","year":"2014","journal-title":"J. Intern. Med."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"126","DOI":"10.1212\/WNL.0000000000004826","article-title":"Practice Guideline Update Summary: Mild Cognitive Impairment Report of Theguideline Development, Dissemination, and Implementation","volume":"90","author":"Petersen","year":"2018","journal-title":"Neurology"},{"key":"ref_11","doi-asserted-by":"crossref","unstructured":"Rossini, P.M., Miraglia, F., Al\u00f9, F., Cotelli, M., Ferreri, F., Di Iorio, R., Iodice, F., and Vecchio, F. (2020). Neurophysiological Hallmarks of Neurodegenerative Cognitive Decline: The Study of Brain Connectivity as a Biomarker of Early Dementia. J. Pers. Med., 10.","DOI":"10.3390\/jpm10020034"},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"263","DOI":"10.1016\/j.jalz.2011.03.005","article-title":"The Diagnosis of Dementia Due to Alzheimer\u2019s Disease: Recommendations from the National Institute on Aging-Alzheimer\u2019s Association Workgroups on Diagnostic Guidelines for Alzheimer\u2019s Disease","volume":"7","author":"McKhann","year":"2011","journal-title":"Alzheimer\u2019s Dement."},{"key":"ref_13","doi-asserted-by":"crossref","unstructured":"Molinuevo, J.L., Ayton, S., Batrla, R., Bednar, M.M., Bittner, T., Cummings, J., Fagan, A.M., Hampel, H., Mielke, M.M., and Mikulskis, A. (2018). Current State of Alzheimer\u2019s Fluid Biomarkers, Springer.","DOI":"10.1007\/s00401-018-1932-x"},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"249","DOI":"10.1038\/nature25456","article-title":"High Performance Plasma Amyloid-\u03b2 Biomarkers for Alzheimer\u2019s Disease","volume":"554","author":"Nakamura","year":"2018","journal-title":"Nature"},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"277","DOI":"10.1038\/s41591-018-0304-3","article-title":"Serum Neurofilament Dynamics Predicts Neurodegeneration and Clinical Progression in Presymptomatic Alzheimer\u2019s Disease","volume":"25","author":"Preische","year":"2019","journal-title":"Nat. Med."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"422","DOI":"10.1016\/S1474-4422(20)30071-5","article-title":"Blood Phosphorylated Tau 181 as a Biomarker for Alzheimer\u2019s Disease: A Diagnostic Performance and Prediction Modelling Study Using Data from Four Prospective Cohorts","volume":"19","author":"Karikari","year":"2020","journal-title":"Lancet Neurol."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"772","DOI":"10.1001\/jama.2020.12134","article-title":"Discriminative Accuracy of Plasma Phospho-Tau217 for Alzheimer Disease vs Other Neurodegenerative Disorders","volume":"324","author":"Palmqvist","year":"2020","journal-title":"JAMA\u2014J. Am. Med. Assoc."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"296","DOI":"10.1038\/s41380-020-0721-9","article-title":"Biomarkers for Alzheimer\u2019s Disease\u2014Preparing for a New Era of Disease-Modifying Therapies","volume":"26","author":"Zetterberg","year":"2021","journal-title":"Mol. Psychiatry"},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"156","DOI":"10.1016\/S1047-8477(02)00625-1","article-title":"Assemblies of Alzheimer\u2019s Peptides A\u03b225\u201335 and A\u03b231\u201335: Reverse-Turn Conformation and Side-Chain Interactions Revealed by X-Ray Diffraction","volume":"141","author":"Bond","year":"2003","journal-title":"J. Struct. Biol."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"1154","DOI":"10.1016\/S0891-5849(01)00510-X","article-title":"New Evidence That the Alzheimer \u03b2-Amyloid Peptide Does Not Spontaneously Form Free Radicals: An ESR Study Using a Series of Spin-Traps","volume":"30","author":"Turnbull","year":"2001","journal-title":"Free Radic. Biol. Med."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"819","DOI":"10.1021\/bi035728h","article-title":"Both the <scp>d -(+) and <scp>l<\/Scp> -(\u2212) Enantiomers of Nicotine Inhibit A\u03b2 Aggregation and Cytotoxicity","volume":"43","author":"Moore","year":"2004","journal-title":"Biochemistry"},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"1220","DOI":"10.1093\/brain\/awaa054","article-title":"Plasma Tau, Neurofilament Light Chain and Amyloid-\u03b2 Levels and Risk of Dementia; a Population-Based Cohort Study","volume":"143","author":"Ghanbari","year":"2020","journal-title":"Brain"},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1186\/s13195-021-00944-y","article-title":"Comparison of Plasma Neurofilament Light and Total Tau as Neurodegeneration Markers: Associations with Cognitive and Neuroimaging Outcomes","volume":"13","author":"Marks","year":"2021","journal-title":"Alzheimers. Res. Ther."},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"60","DOI":"10.1016\/j.neulet.2017.04.027","article-title":"Plasma Neurofilament Light Chain Levels in Alzheimer\u2019s Disease","volume":"650","author":"Zhou","year":"2017","journal-title":"Neurosci. Lett."},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"fcac155","DOI":"10.1093\/braincomms\/fcac155","article-title":"Plasma Biomarkers for Prognosis of Cognitive Decline in Patients with Mild Cognitive Impairment","volume":"4","author":"Magdamo","year":"2022","journal-title":"Brain Commun."},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"e102","DOI":"10.1093\/nar\/gkr424","article-title":"Homogeneous Antibody-Based Proximity Extension Assays Provide Sensitive and Specific Detection of Low-Abundant Proteins in Human Blood","volume":"39","author":"Lundberg","year":"2011","journal-title":"Nucleic Acids Res."},{"key":"ref_27","doi-asserted-by":"crossref","unstructured":"Assarsson, E., Lundberg, M., Holmquist, G., Bj\u00f6rkesten, J., Bucht Thorsen, S., Ekman, D., Eriksson, A., Rennel Dickens, E., Ohlsson, S., and Edfeldt, G. (2014). Homogenous 96-Plex PEA Immunoassay Exhibiting High Sensitivity, Specificity, and Excellent Scalability. PLoS ONE, 9.","DOI":"10.1371\/journal.pone.0095192"},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1038\/s41598-020-65038-5","article-title":"CDH6 and HAGH Protein Levels in Plasma Associate with Alzheimer\u2019s Disease in APOE \u03954 Carriers","volume":"10","author":"Ahmad","year":"2020","journal-title":"Sci. Rep."},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"169","DOI":"10.1186\/s40478-019-0795-2","article-title":"Multiplex Proteomics Identifies Novel CSF and Plasma Biomarkers of Early Alzheimer\u2019s Disease","volume":"7","author":"Whelan","year":"2019","journal-title":"Acta Neuropathol. Commun."},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"1965","DOI":"10.1038\/s41598-021-81705-7","article-title":"Accelerated Inflammatory Aging in Alzheimer\u2019s Disease and Its Relation to Amyloid, Tau, and Cognition","volume":"11","author":"Cullen","year":"2021","journal-title":"Sci. Rep."},{"key":"ref_31","doi-asserted-by":"crossref","unstructured":"Ehtewish, H., Arredouani, A., and El-Agnaf, O. (2022). Diagnostic, Prognostic, and Mechanistic Biomarkers of Diabetes Mellitus-Associated Cognitive Decline. Int. J. Mol. Sci., 23.","DOI":"10.3390\/ijms23116144"},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"88","DOI":"10.1002\/alz.12369","article-title":"Large-Scale Plasma Proteomic Profiling Identifies a High-Performance Biomarker Panel for Alzheimer\u2019s Disease Screening and Staging","volume":"18","author":"Jiang","year":"2022","journal-title":"Alzheimer\u2019s Dement."},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"473","DOI":"10.1038\/s43587-021-00064-0","article-title":"Large-Scale Plasma Proteomic Analysis Identifies Proteins and Pathways Associated with Dementia Risk","volume":"1","author":"Walker","year":"2021","journal-title":"Nat. Aging"},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"337","DOI":"10.1097\/WAD.0b013e31827b60d2","article-title":"Plasma Proteomics for the Identification of Alzheimer\u2019s Disease","volume":"27","author":"Guo","year":"2013","journal-title":"Alzheimer Dis. Assoc. Disord."},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"642","DOI":"10.4049\/jimmunol.169.2.642","article-title":"Cutting Edge: IL-17D, a Novel Member of the IL-17 Family, Stimulates Cytokine Production and Inhibits Hemopoiesis","volume":"169","author":"Starnes","year":"2002","journal-title":"J. Immunol."},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"105655","DOI":"10.1016\/j.nbd.2022.105655","article-title":"Multi-Transcriptomic Analysis Points to Early Organelle Dysfunction in Human Astrocytes in Alzheimer\u2019s Disease","volume":"166","author":"Galea","year":"2022","journal-title":"Neurobiol. Dis."},{"key":"ref_37","doi-asserted-by":"crossref","unstructured":"Roach, J.C., Edens, L., Markewych, D.R., Rapozo, M.K., Hara, J., Glusman, G., Funk, C., Bramen, J., Baloni, P., and Shankle, W.R. (2022). A Multimodal Intervention for Alzheimer\u2019s Disease Results in Multifaceted Systemic Effects Reflected in Blood and Ameliorates Functional and Cognitive Outcomes. medRxiv, 03424200.","DOI":"10.1101\/2022.09.27.22280385"},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"3544","DOI":"10.1111\/bph.14586","article-title":"Neutralization of IL-17 Rescues Amyloid-\u03b2-Induced Neuroinflammation and Memory Impairment","volume":"176","author":"Cristiano","year":"2019","journal-title":"Br. J. Pharmacol."},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"57","DOI":"10.1016\/j.blre.2016.08.004","article-title":"Placental Growth Factor: What Hematologists Need to Know","volume":"31","author":"Newell","year":"2017","journal-title":"Blood Rev."},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"215","DOI":"10.1007\/s10456-008-9114-4","article-title":"The Discovery of the Placental Growth Factor and Its Role in Angiogenesis: A Historical Review","volume":"11","author":"Ribatti","year":"2008","journal-title":"Angiogenesis"},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"863","DOI":"10.1002\/acn3.763","article-title":"CSF Placental Growth Factor\u2014a Novel Candidate Biomarker of Frontotemporal Dementia","volume":"6","author":"Hansson","year":"2019","journal-title":"Ann. Clin. Transl. Neurol."},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"888","DOI":"10.1038\/s41380-019-0458-5","article-title":"Brain Expression of the Vascular Endothelial Growth Factor Gene Family in Cognitive Aging and Alzheimer\u2019s Disease","volume":"26","author":"Mahoney","year":"2021","journal-title":"Mol. Psychiatry"},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"67","DOI":"10.1002\/alz.12639","article-title":"Examining the Association between Blood-Based Biomarkers and Human Post Mortem Neuropathology in the University of Kentucky Alzheimer\u2019s Disease Research Center Autopsy Cohort","volume":"19","author":"Winder","year":"2022","journal-title":"Alzheimer\u2019s Dement."},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"e041795","DOI":"10.1002\/alz.041795","article-title":"White Matter Lesions Are Associated with CSF Biomarkers of Neuroinflammation in Prodromal Alzheimer\u2019s Disease","volume":"16","author":"Gertje","year":"2020","journal-title":"Alzheimer\u2019s Dement."},{"key":"ref_45","first-page":"e052995","article-title":"CSF and Plasma Placental Growth Factor as a Biomarker for Small-Vessel Damage in VCID","volume":"17","author":"Sudduth","year":"2021","journal-title":"Alzheimers. Dement."},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"227","DOI":"10.3389\/fncel.2019.00227","article-title":"Wnt Signaling Deregulation in the Aging and Alzheimer\u2019s Brain","volume":"13","author":"Palomer","year":"2019","journal-title":"Front. Cell. Neurosci."},{"key":"ref_47","doi-asserted-by":"crossref","first-page":"101","DOI":"10.1016\/j.brainres.2008.12.039","article-title":"Hippocampal Gene Expression Changes during Age-Related Cognitive Decline","volume":"1256","author":"Pawlowski","year":"2009","journal-title":"Brain Res."},{"key":"ref_48","doi-asserted-by":"crossref","first-page":"58","DOI":"10.1016\/j.pharmthera.2008.01.004","article-title":"The Wnt Signaling Pathway: Aging Gracefully as a Protectionist?","volume":"118","author":"Maiese","year":"2008","journal-title":"Pharmacol. Ther."},{"key":"ref_49","doi-asserted-by":"crossref","first-page":"23","DOI":"10.4161\/cc.5.1.2305","article-title":"R-Spondin Proteins: A Novel Link to \u03b2-Catenin Activation","volume":"5","author":"Kim","year":"2006","journal-title":"Cell Cycle"},{"key":"ref_50","doi-asserted-by":"crossref","first-page":"a015081","DOI":"10.1101\/cshperspect.a015081","article-title":"Secreted and Transmembrane Wnt Inhibitors and Activators","volume":"5","author":"Cruciat","year":"2013","journal-title":"Cold Spring Harb. Perspect. Biol."},{"key":"ref_51","doi-asserted-by":"crossref","first-page":"96","DOI":"10.1001\/archneurol.2011.642","article-title":"Proteomic Changes in Cerebrospinal Fluid of Presymptomatic and Affected Persons Carrying Familial Alzheimer Disease Mutations","volume":"69","author":"Ringman","year":"2012","journal-title":"Arch. Neurol."},{"key":"ref_52","first-page":"e12240","article-title":"Identification of Plasma Proteins Relating to Brain Neurodegeneration and Vascular Pathology in Cognitively Normal Individuals","volume":"13","author":"Shi","year":"2021","journal-title":"Alzheimer\u2019s Dement. Diagn. Assess. Dis. Monit."},{"key":"ref_53","doi-asserted-by":"crossref","first-page":"822","DOI":"10.3389\/fendo.2019.00822","article-title":"IGFBP-2 Signaling in the Brain: From Brain Development to Higher Order Brain Functions","volume":"10","author":"Khan","year":"2019","journal-title":"Front. Endocrinol. Lausanne"},{"key":"ref_54","doi-asserted-by":"crossref","first-page":"1160","DOI":"10.1097\/01.WCB.0000087091.01171.AE","article-title":"Neuroprotective Effects of Insulin-like Growth Factor-Binding Protein Ligand Inhibitors in Vitro and in Vivo","volume":"23","author":"Mackay","year":"2003","journal-title":"J. Cereb. Blood Flow Metab."},{"key":"ref_55","doi-asserted-by":"crossref","first-page":"637","DOI":"10.3233\/JAD-150351","article-title":"Increased Cerebrospinal Fluid Level of Insulin-like Growth Factor-II in Male Patients with Alzheimer\u2019s Disease","volume":"48","author":"Johansson","year":"2015","journal-title":"J. Alzheimer\u2019s Dis."},{"key":"ref_56","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1186\/1471-2377-14-64","article-title":"Changes in Cerebrospinal Fluid and Blood Plasma Levels of IGF-II and Its Binding Proteins in Alzheimer\u2019s Disease: An Observational Study","volume":"14","author":"Hertze","year":"2014","journal-title":"BMC Neurol."},{"key":"ref_57","doi-asserted-by":"crossref","unstructured":"Toledo, J.B., Da, X., Bhatt, P., Wolk, D.A., Arnold, S.E., Shaw, L.M., Trojanowski, J.Q., and Davatzikos, C. (2013). Relationship between Plasma Analytes and SPARE-AD Defined Brain Atrophy Patterns in ADNI. PLoS ONE, 8.","DOI":"10.1371\/journal.pone.0055531"},{"key":"ref_58","doi-asserted-by":"crossref","first-page":"1779","DOI":"10.1007\/s11682-016-9636-0","article-title":"Insulin-like Growth Factor Binding Protein-2 Interactions with Alzheimer\u2019s Disease Biomarkers","volume":"11","author":"Lane","year":"2017","journal-title":"Brain Imaging Behav."},{"key":"ref_59","doi-asserted-by":"crossref","first-page":"1313","DOI":"10.3233\/JAD-170263","article-title":"Peripheral versus Central Index of Metabolic Dysfunction and Associations with Clinical and Pathological Outcomes in Alzheimer\u2019s Disease","volume":"60","author":"McLimans","year":"2017","journal-title":"J. Alzheimer\u2019s Dis."},{"key":"ref_60","doi-asserted-by":"crossref","unstructured":"Lin, H., Himali, J.J., Satizabal, C.L., Beiser, A.S., Levy, D., Benjamin, E.J., Gonzales, M.M., Ghosh, S., Vasan, R.S., and Seshadri, S. (2022). Identifying Blood Biomarkers for Dementia Using Machine Learning Methods in the Framingham Heart Study. Cells, 11.","DOI":"10.3390\/cells11091506"},{"key":"ref_61","doi-asserted-by":"crossref","first-page":"1659","DOI":"10.1002\/acn3.50854","article-title":"Circulating IGFBP-2: A Novel Biomarker for Incident Dementia","volume":"6","author":"McGrath","year":"2019","journal-title":"Ann. Clin. Transl. Neurol."},{"key":"ref_62","doi-asserted-by":"crossref","first-page":"549","DOI":"10.3233\/JAD-220256","article-title":"A Novel Panel of Plasma Proteins Predicts Progression in Prodromal Alzheimer\u2019s Disease","volume":"88","author":"Veloso","year":"2022","journal-title":"J. Alzheimer\u2019s Dis."},{"key":"ref_63","doi-asserted-by":"crossref","first-page":"414","DOI":"10.3389\/fnagi.2018.00414","article-title":"Blood-Derived Plasma Protein Biomarkers for Alzheimer\u2019s Disease in Han Chinese","volume":"10","author":"Cheng","year":"2018","journal-title":"Front. Aging Neurosci."},{"key":"ref_64","doi-asserted-by":"crossref","first-page":"135","DOI":"10.31887\/DCNS.2009.11.2\/bdubois","article-title":"Early Detection of Alzheimer\u2019s Disease: New Diagnostic Criteria","volume":"11","author":"Dubois","year":"2009","journal-title":"Dialogues Clin. Neurosci."},{"key":"ref_65","doi-asserted-by":"crossref","first-page":"250","DOI":"10.1212\/WNL.43.2.250","article-title":"Vascular Dementia: Diagnostic Criteria for Research Studies: Report of the NINDS-AIREN International Workshop","volume":"43","author":"Roman","year":"1993","journal-title":"Neurology"},{"key":"ref_66","doi-asserted-by":"crossref","first-page":"972","DOI":"10.1093\/bioinformatics\/bty710","article-title":"Variable Selection and Validation in Multivariate Modelling","volume":"35","author":"Shi","year":"2019","journal-title":"Bioinformatics"},{"key":"ref_67","doi-asserted-by":"crossref","first-page":"1","DOI":"10.18637\/jss.v036.i11","article-title":"Feature Selection with the Boruta Package","volume":"36","author":"Kursa","year":"2010","journal-title":"J. Stat. Softw."},{"key":"ref_68","doi-asserted-by":"crossref","first-page":"1903","DOI":"10.21105\/joss.01903","article-title":"Mlr3: A Modern Object-Oriented Machine Learning Framework in R","volume":"4","author":"Lang","year":"2019","journal-title":"J. Open Source Softw."}],"container-title":["International Journal of Molecular Sciences"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/1422-0067\/24\/9\/8117\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,10]],"date-time":"2025-10-10T19:27:35Z","timestamp":1760124455000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/1422-0067\/24\/9\/8117"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2023,5,1]]},"references-count":68,"journal-issue":{"issue":"9","published-online":{"date-parts":[[2023,5]]}},"alternative-id":["ijms24098117"],"URL":"https:\/\/doi.org\/10.3390\/ijms24098117","relation":{},"ISSN":["1422-0067"],"issn-type":[{"value":"1422-0067","type":"electronic"}],"subject":[],"published":{"date-parts":[[2023,5,1]]}}}