{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,1]],"date-time":"2026-10-01T16:01:14Z","timestamp":1790870474406,"version":"4.1.0"},"reference-count":35,"publisher":"MDPI AG","issue":"18","license":[{"start":{"date-parts":[[2023,9,6]],"date-time":"2023-09-06T00:00:00Z","timestamp":1693958400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"TTY BIOPHARM CO., LTD."},{"name":"SHIUN CHAO BIOPHARM CO., LTD."},{"name":"National Taiwan Normal University"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>The number of elderly dogs is increasing significantly worldwide, and many elderly dogs develop canine cognitive dysfunction syndrome (CCDS). CCDS is the canine analog of Alzheimer\u2019s disease (AD) in humans. It is very important to develop techniques for detecting CDDS in dogs. Thus, we used the detection of neurofilament light chains (NfL) in plasma as a blood-based biomarker for the early diagnosis of canine Alzheimer\u2019s disease using immunomagnetic reduction (IMR) technology by immobilizing NfL antibodies on magnetic nanoparticles. According to the 50-point CCDS rating scale, we divided 36 dogs into 15 with CCDS and 21 without the disease. The results of our IMR assay showed that the plasma NfL levels of dogs with CCDS were significantly increased compared to normal dogs (p &lt; 0.01). By plasma biochemical analysis, we further confirmed that the liver and renal dysfunction biomarkers of dogs with CCDS were significantly elevated compared to normal dogs (p &lt; 0.01\u20130.05). On the basis of our preliminary study, we propose that IMR technology could be an ideal biosensor for detecting plasma NfL for the early diagnosis of CCDS.<\/jats:p>","DOI":"10.3390\/ijms241813771","type":"journal-article","created":{"date-parts":[[2023,9,7]],"date-time":"2023-09-07T09:51:37Z","timestamp":1694080297000},"page":"13771","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":12,"title":["Plasma Neurofilament Light Chains as Blood-Based Biomarkers for Early Diagnosis of Canine Cognitive Dysfunction Syndrome"],"prefix":"10.3390","volume":"24","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-4470-2448","authenticated-orcid":false,"given":"Chung-Hsin","family":"Wu","sequence":"first","affiliation":[{"name":"School of Life Science, National Taiwan Normal University, Taipei 106, Taiwan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xun-Sheng","family":"Pan","sequence":"additional","affiliation":[{"name":"Zaixing Animal Hospital, Taipei 116, Taiwan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Li-Yu","family":"Su","sequence":"additional","affiliation":[{"name":"Department of Physiology, College of Medicine, National Taiwan University, Taipei 106, Taiwan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shieh-Yueh","family":"Yang","sequence":"additional","affiliation":[{"name":"MagQu Co., Ltd., New Taipei City 112, Taiwan"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2023,9,6]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"551895","DOI":"10.3389\/fvets.2020.551895","article-title":"Novel Diagnostic Tools for Identifying Cognitive Impairment in Dogs: Behavior, Biomarkers, and Pathology","volume":"7","author":"Vikartovska","year":"2021","journal-title":"Front. Vet. Sci."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"1384","DOI":"10.1016\/j.bbadis.2013.03.016","article-title":"canine model of human aging and Alzheimer\u2019s disease","volume":"1832","author":"Head","year":"2013","journal-title":"Biochim. Biophys. Acta"},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"8205","DOI":"10.1523\/JNEUROSCI.1339-04.2004","article-title":"Frontal lobe volume, function, and beta-amyloid pathology in a canine model of aging","volume":"24","author":"Tapp","year":"2004","journal-title":"J. Neurosci. Off. J. Soc. Neurosci."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"39","DOI":"10.1016\/j.neurobiolaging.2006.09.018","article-title":"Region specific neuron loss in the aged canine hippocampus is reduced by enrichment","volume":"29","author":"Head","year":"2008","journal-title":"Neurobiol. Aging"},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"331","DOI":"10.1016\/j.tvjl.2010.05.014","article-title":"The canine cognitive dysfunction rating scale (CCDR): A data-driven and ecologically relevant assessment tool","volume":"188","author":"Salvin","year":"2011","journal-title":"Vet. J."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"603","DOI":"10.1016\/j.pnpbp.2005.01.017","article-title":"Severe cognitive impairment correlates with higher cerebrospinal fluid levels of lactate and pyruvate in a canine model of senile dementia","volume":"29","author":"Pugliese","year":"2005","journal-title":"Prog. Neuro-Psychopharmacol. Biol. Psychiatry"},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"590","DOI":"10.1016\/j.exger.2011.02.013","article-title":"Plasma \u03b2-amyloid peptides in canine aging and cognitive dysfunction as a model of Alzheimer\u2019s disease","volume":"46","author":"Rosado","year":"2011","journal-title":"Exp. Gerontol."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"210","DOI":"10.5455\/OVJ.2021.v11.i2.4","article-title":"Periodontal disease is associated with cognitive dysfunction in aging dogs: A blinded prospective comparison of visual periodontal and cognitive questionnaire scores","volume":"11","author":"Dewey","year":"2021","journal-title":"Open Vet. J."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"763","DOI":"10.3233\/JAD-160434","article-title":"Young to Middle-Aged Dogs with High Amyloid-\u03b2 Levels in Cerebrospinal Fluid are Impaired on Learning in Standard Cognition tests","volume":"56","author":"Borghys","year":"2017","journal-title":"J. Alzheimers Dis. JAD"},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"277","DOI":"10.1038\/s41591-018-0304-3","article-title":"Dominantly Inherited Alzheimer Network. 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_11","doi-asserted-by":"crossref","first-page":"3143","DOI":"10.1007\/s12035-020-01951-0","article-title":"Plasma Neurofilament Light Chain as a Translational Biomarker of Aging and Neurodegeneration in Dogs","volume":"57","author":"Panek","year":"2020","journal-title":"Mol. Neurobiol."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"936","DOI":"10.1136\/jnnp.2006.107326","article-title":"CSF neurofilament proteins in the differential diagnosis of dementia","volume":"78","author":"Jansen","year":"2007","journal-title":"J. Neurol. Neurosurg. Psychiatry"},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"1827","DOI":"10.1212\/WNL.0000000000003246","article-title":"ADNI Investigators. Plasma tau in Alzheimer disease","volume":"87","author":"Mattsson","year":"2016","journal-title":"Neurology"},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"500","DOI":"10.1021\/cn200028j","article-title":"Biofunctionalized magnetic nanoparticles for specifically detecting biomarkers of Alzheimer\u2019s disease in vitro","volume":"2","author":"Yang","year":"2011","journal-title":"ACS Chem. Neurosci."},{"key":"ref_15","doi-asserted-by":"crossref","unstructured":"Liu, H.C., Lin, W.C., Chiu, M.J., Lu, C.H., Lin, C.Y., and Yang, S.Y. (2020). Development of an assay of plasma neurofilament light chain utilizing immunomagnetic reduction technology. PLoS ONE, 15.","DOI":"10.1371\/journal.pone.0234519"},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"2013","DOI":"10.1046\/j.1471-4159.1996.67052013.x","article-title":"Patients with amyotrophic lateral sclerosis and other neurodegenerative diseases have increased levels of neurofilament protein in CSF","volume":"67","author":"Rosengren","year":"1996","journal-title":"J. Neurochem."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"179","DOI":"10.1016\/j.jim.2004.11.015","article-title":"An enzyme immunoassay to quantify neurofilament light chain in cerebrospinal fluid","volume":"296","author":"Rosengren","year":"2005","journal-title":"J. Immunol. Methods"},{"key":"ref_18","doi-asserted-by":"crossref","unstructured":"Gaiottino, J., Norgren, N., Dobson, R., Topping, J., Nissim, A., Malaspina, A., Bestwick, J.P., Monsch, A.U., Regeniter, A., and Lindberg, R.L. (2013). Increased neurofilament light chain blood levels in neurodegenerative neurological diseases. PLoS ONE, 8.","DOI":"10.1371\/journal.pone.0075091"},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"557","DOI":"10.1001\/jamaneurol.2016.6117","article-title":"Association of Plasma Neurofilament Light with Neurodegeneration in Patients with Alzheimer Disease","volume":"74","author":"Mattsson","year":"2017","journal-title":"JAMA Neurol."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"1329","DOI":"10.1212\/WNL.0000000000003154","article-title":"Serum neurofilament light chain protein is a measure of disease intensity in frontotemporal dementia","volume":"87","author":"Rohrer","year":"2016","journal-title":"Neurology"},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"1655","DOI":"10.1515\/cclm-2015-1195","article-title":"Comparison of three analytical platforms for quantification of the neurofilament light chain in blood samples: ELISA, electrochemiluminescence immunoassay and Simoa","volume":"54","author":"Kuhle","year":"2016","journal-title":"Clin. Chem. Lab. Med."},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"1865","DOI":"10.1111\/jvim.16184","article-title":"Neurofilament light chain as a biomarker of meningoencephalitis of unknown etiology in dogs","volume":"35","author":"Yun","year":"2021","journal-title":"J. Vet. Intern. Med."},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"1142","DOI":"10.2174\/156720512804142967","article-title":"New assay for old markers-plasma beta amyloid of mild cognitive impairment and Alzheimer\u2019s disease","volume":"9","author":"Chiu","year":"2012","journal-title":"Curr. Alzheimer Res."},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"162","DOI":"10.1186\/s13195-020-00728-w","article-title":"Comparison of ELISA- and SIMOA-based quantification of plasma A\u03b2 ratios for early detection of cerebral amyloidosis","volume":"12","author":"Schaeverbeke","year":"2020","journal-title":"Alzheimers Res. Ther."},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"9304","DOI":"10.1038\/s41598-017-09009-3","article-title":"Analytical performance of reagent for assaying tau protein in human plasma and feasibility study screening neurodegenerative diseases","volume":"7","author":"Yang","year":"2017","journal-title":"Sci. Rep."},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"11772719211053449","DOI":"10.1177\/11772719211053449","article-title":"Serum Neurofilament Light as a Biomarker of Traumatic Brain Injury in the Presence of Concomitant Peripheral Injury","volume":"16","author":"Wong","year":"2021","journal-title":"Biomark. Insights"},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"135593","DOI":"10.1016\/j.neulet.2020.135593","article-title":"Neurofilament light plasma concentration positively associates with age and negatively associates with weight and height in the dog","volume":"744","author":"Perino","year":"2021","journal-title":"Neurosci. Lett."},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"1367","DOI":"10.3233\/JAD-215562","article-title":"Use of Cognitive Testing, Questionnaires, and Plasma Biomarkers to Quantify Cognitive Impairment in an Aging Pet Dog Population","volume":"87","author":"Fefer","year":"2020","journal-title":"J. Alzheimers Dis. JAD"},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"601","DOI":"10.1016\/S1474-4422(17)30124-2","article-title":"Neurofilament light protein in blood as a potential biomarker of neurodegeneration in Huntington\u2019s disease: A retrospective cohort analysis","volume":"16","author":"Byrne","year":"2017","journal-title":"Lancet. Neurol."},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"13984","DOI":"10.1038\/s41598-019-50315-9","article-title":"Plasma A\u03b242 and Total Tau Predict Cognitive Decline in Amnestic Mild Cognitive Impairment","volume":"9","author":"Chen","year":"2019","journal-title":"Sci. Rep."},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"941","DOI":"10.1016\/j.cvsm.2016.06.010","article-title":"Symmetric Dimethylarginine: Improving the Diagnosis and Staging of Chronic Kidney Disease in Small Animals","volume":"46","author":"Relford","year":"2016","journal-title":"Vet. Clin. N. Am. Small Anim. Pract."},{"key":"ref_32","first-page":"225","article-title":"Immunoanalytical characteristics of C-reactive protein and high sensitivity C-reactive protein. Caract\u00e9ristiques immunoanalytiques de la prot\u00e9ine C-r\u00e9active et de la prot\u00e9ine C-r\u00e9active ultrasensible","volume":"75","author":"Moutachakkir","year":"2017","journal-title":"Ann. Biol. Clin."},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"29","DOI":"10.1111\/vcp.13100","article-title":"Measurement and clinical applications of C-reactive protein in gastrointestinal diseases of dogs","volume":"50","author":"Covin","year":"2022","journal-title":"Vet. Clin. Pathol."},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"870","DOI":"10.1136\/jnnp-2018-320106","article-title":"Neurofilament light chain as a biomarker in neurological disorders","volume":"90","author":"Gaetani","year":"2019","journal-title":"J. Neurol. Neurosurg. Psychiatry"},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"2688","DOI":"10.1016\/j.jmmm.2008.05.048","article-title":"Dual immobilization and magnetic manipulation of magnetic nanoparticles","volume":"320","author":"Yang","year":"2008","journal-title":"J. Magn. Magn. Mater."}],"container-title":["International Journal of Molecular Sciences"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/1422-0067\/24\/18\/13771\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,10]],"date-time":"2025-10-10T20:46:25Z","timestamp":1760129185000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/1422-0067\/24\/18\/13771"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2023,9,6]]},"references-count":35,"journal-issue":{"issue":"18","published-online":{"date-parts":[[2023,9]]}},"alternative-id":["ijms241813771"],"URL":"https:\/\/doi.org\/10.3390\/ijms241813771","relation":{},"ISSN":["1422-0067"],"issn-type":[{"value":"1422-0067","type":"electronic"}],"subject":[],"published":{"date-parts":[[2023,9,6]]}}}