{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,1]],"date-time":"2026-07-01T23:33:26Z","timestamp":1782948806222,"version":"3.54.5"},"reference-count":46,"publisher":"MDPI AG","issue":"10","license":[{"start":{"date-parts":[[2024,10,17]],"date-time":"2024-10-17T00:00:00Z","timestamp":1729123200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100014188","name":"National Research Foundation of Korea","doi-asserted-by":"publisher","award":["2021M3H4A4079521"],"award-info":[{"award-number":["2021M3H4A4079521"]}],"id":[{"id":"10.13039\/501100014188","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100014188","name":"National Research Foundation of Korea","doi-asserted-by":"publisher","award":["NRF-2018R1D1A1B05049787"],"award-info":[{"award-number":["NRF-2018R1D1A1B05049787"]}],"id":[{"id":"10.13039\/501100014188","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100003725","name":"Korean government","doi-asserted-by":"publisher","award":["2021M3H4A4079521"],"award-info":[{"award-number":["2021M3H4A4079521"]}],"id":[{"id":"10.13039\/501100003725","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100003725","name":"Korean government","doi-asserted-by":"publisher","award":["NRF-2018R1D1A1B05049787"],"award-info":[{"award-number":["NRF-2018R1D1A1B05049787"]}],"id":[{"id":"10.13039\/501100003725","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Biosensors"],"abstract":"<jats:p>Monitoring the progression of Alzheimer\u2019s disease (AD) is crucial for mitigating dementia symptoms, alleviating pain, and improving mobility. Traditionally, AD biomarkers like amyloid plaques are predominantly identified in cerebrospinal fluid (CSF) due to their concentrated presence. However, detecting these markers in blood is hindered by the blood\u2013brain barrier (BBB), resulting in lower concentrations. To address this challenge and identify pertinent AD biomarkers\u2014specifically amyloid plaques and apolipoprotein E4 (ApoE4)\u2014in blood plasma, we propose an innovative approach. This involves enhancing a screen-printed carbon electrode (SPCE) with an immobilization matrix comprising gold nanostars (AuNSs) coated with chitosan. Morphological and electrical analyses confirmed superior dispersion and conductivity with 0.5% chitosan, supported by UV\u2013Vis spectroscopy, cyclic voltammetry, and Nyquist plots. Subsequent clinical assays measured electrical responses to quantify amyloid-\u03b2 42 (A\u03b242) (15.63\u20131000 pg\/mL) and APoE4 levels (0.41 to 40 ng\/mL) in human blood plasma samples. Differential pulse voltammetry (DPV) responses exhibited peak currents proportional to biomarker concentrations, demonstrating high linear correlations (0.985 for A\u03b242 and 0.919 for APoE4) with minimal error bars. Cross-reactivity tests with mixed solutions of amyloid-\u03b2 40 (A\u03b240), A\u03b242, and ApoE4 indicated minimal interference between biomarkers (&lt;3% variation), further confirming the high specificity of the developed sensor. Validation studies demonstrated a strong concurrence with the gold-standard enzyme-linked immunosorbent assay (ELISA), while interference tests indicated a minimal variation in peak currents. This improved device presents promising potential as a point-of-care system, offering a less invasive, cost-effective, and simplified approach to detecting and tracking the progression of AD. The substantial surface binding area further supports the efficacy of our method, offering a promising avenue for advancing AD diagnostics.<\/jats:p>","DOI":"10.3390\/bios14100510","type":"journal-article","created":{"date-parts":[[2024,10,18]],"date-time":"2024-10-18T06:46:52Z","timestamp":1729234012000},"page":"510","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":17,"title":["Electrochemical Analysis of Amyloid Plaques and ApoE4 with Chitosan-Coated Gold Nanostars for Alzheimer\u2019s Detection"],"prefix":"10.3390","volume":"14","author":[{"ORCID":"https:\/\/orcid.org\/0009-0006-7661-9557","authenticated-orcid":false,"given":"Min-Kyung","family":"Shin","sequence":"first","affiliation":[{"name":"Department of Electrical and Computer Engineering, Sungkyunkwan University, Suwon 16419, Republic of Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3839-4423","authenticated-orcid":false,"given":"Ariadna","family":"Schuck","sequence":"additional","affiliation":[{"name":"Department of Electrical and Computer Engineering, Sungkyunkwan University, Suwon 16419, Republic of Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Minhee","family":"Kang","sequence":"additional","affiliation":[{"name":"Biomedical Engineering Research Center, Smart Healthcare Research Institute, Samsung Medical Center, School of Medicine, Sungkyunkwan University, Seoul 06351, Republic of Korea"},{"name":"Department of Medical Device Management and Research, Samsung Advanced Institute for Health Sciences & Technology (SAIHST), Sungkyunkwan University, Seoul 06351, Republic of Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2986-2686","authenticated-orcid":false,"given":"Yong-Sang","family":"Kim","sequence":"additional","affiliation":[{"name":"Department of Electrical and Computer Engineering, Sungkyunkwan University, Suwon 16419, Republic of Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2024,10,17]]},"reference":[{"key":"ref_1","first-page":"e688","article-title":"Validation of Plasma Amyloid-\u03b2 42\/40 for Detecting Alzheimer Disease Amyloid Plaques","volume":"98","author":"Li","year":"2022","journal-title":"Neurology"},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"103","DOI":"10.1186\/s12984-019-0576-y","article-title":"Mobility assessment in people with Alzheimer disease using smartphone sensors","volume":"16","year":"2019","journal-title":"J. Neuroeng. Rehabil."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"2140","DOI":"10.1021\/acssensors.9b00974","article-title":"Robust and Universal SERS Sensing Platform for Multiplexed Detection of Alzheimer\u2019s Disease Core Biomarkers Using PAapt-AuNPs Conjugates","volume":"4","author":"Zhang","year":"2019","journal-title":"ACS Sens."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"279","DOI":"10.1016\/j.bios.2013.10.069","article-title":"On-chip magneto-immunoassay for Alzheimer\u2019s biomarker electrochemical detection by using quantum dots as labels","volume":"54","author":"Miserere","year":"2014","journal-title":"Biosens. Bioelectron."},{"key":"ref_5","doi-asserted-by":"crossref","unstructured":"Zhou, Y., Zhang, H., Liu, L., Li, C., Chang, Z., Zhu, X., Ye, B., and Xu, M. (2016). Fabrication of an antibody-aptamer sandwich assay for electrochemical evaluation of levels of \u03b2-amyloid oligomers. Sci. Rep., 6.","DOI":"10.1038\/srep35186"},{"key":"ref_6","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_7","doi-asserted-by":"crossref","first-page":"287","DOI":"10.1016\/j.neuron.2009.06.026","article-title":"The Role of Apolipoprotein E in Alzheimer\u2019s Disease","volume":"63","author":"Kim","year":"2009","journal-title":"Neuron"},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"19813","DOI":"10.1073\/pnas.0905007106","article-title":"Comparison of Alzheimer A\u03b2(1\u201340) and A\u03b2(1\u201342) amyloid fibrils reveals similar protofilament structures","volume":"106","author":"Schmidt","year":"2009","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"13170","DOI":"10.1073\/pnas.93.23.13170","article-title":"Evidence that the 42- and 40-amino acid forms of amyloid \u03b2 protein are generated from the \u03b2-amyloid precursor protein by different protease activities","volume":"93","author":"Citron","year":"1996","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"261","DOI":"10.1007\/978-3-319-96445-4_14","article-title":"Blood-Brain Barrier Integrity and Clearance of Amyloid-\u03b2 from the BBB","volume":"1097","author":"Cockerill","year":"2018","journal-title":"Adv. Exp. Med. Biol."},{"key":"ref_11","doi-asserted-by":"crossref","unstructured":"Husain, M.A., Laurent, B., and Plourde, M. (2021). APOE and Alzheimer\u2019s Disease: From Lipid Transport to Physiopathology and Therapeutics. Front. Neurosci., 15.","DOI":"10.3389\/fnins.2021.630502"},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"26","DOI":"10.1016\/j.neubiorev.2018.03.028","article-title":"Interaction between blood-brain barrier and glymphatic system in solute clearance","volume":"90","author":"Verheggen","year":"2018","journal-title":"Neurosci. Biobehav. Rev."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"643","DOI":"10.1111\/joim.12816","article-title":"Biomarkers for Alzheimer\u2019s disease: Current status and prospects for the future","volume":"284","author":"Blennow","year":"2018","journal-title":"J. Intern. Med."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"5644","DOI":"10.1073\/pnas.0600549103","article-title":"Apolipoprotein E4: A causative factor and therapeutic target in neuropathology, including Alzheimer\u2019s disease","volume":"103","author":"Mahley","year":"2006","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"72","DOI":"10.1186\/s13024-022-00574-4","article-title":"ApoE in Alzheimer\u2019s disease: Pathophysiology and therapeutic strategies","volume":"17","author":"Raulin","year":"2022","journal-title":"Mol. Neurodegener."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"29","DOI":"10.1016\/S0304-3940(97)13394-8","article-title":"Increased plasma apolipoprotein E (apoE) levels in Alzheimer\u2019s disease","volume":"223","author":"Taddei","year":"1997","journal-title":"Neurosci. Lett."},{"key":"ref_17","doi-asserted-by":"crossref","unstructured":"Toyos-Rodr\u00edguez, C., Garc\u00eda-Alonso, F.J., and de la Escosura-Mu\u00f1iz, A. (2020). Electrochemical biosensors based on nanomaterials for early detection of alzheimer\u2019s disease. Sensors, 20.","DOI":"10.3390\/s20174748"},{"key":"ref_18","doi-asserted-by":"crossref","unstructured":"Wang, C., Yu, J.T., Wang, H.F., Jiang, T., Tan, C.C., Meng, X.F., Soares, H.D., and Tan, L. (2014). Meta-analysis of peripheral blood apolipoprotein E levels in alzheimer\u2019s disease. PLoS ONE, 9.","DOI":"10.1371\/journal.pone.0089041"},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"69","DOI":"10.1186\/s12987-020-00230-3","article-title":"A blood\u2013brain barrier overview on structure, function, impairment, and biomarkers of integrity","volume":"17","author":"Kadry","year":"2020","journal-title":"Fluids Barriers CNS"},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"396","DOI":"10.1016\/j.bios.2015.04.068","article-title":"An ultrasensitive electrochemical immunosensor for apolipoprotein E4 based on fractal nanostructures and enzyme amplification","volume":"71","author":"Liu","year":"2015","journal-title":"Biosens. Bioelectron."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"1851","DOI":"10.1021\/acssensors.9b00631","article-title":"Reversible immuno-infrared sensor for the detection of Alzheimer\u2019s disease related biomarkers","volume":"4","author":"Budde","year":"2019","journal-title":"ACS Sens."},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"119","DOI":"10.1038\/s41467-019-13901-z","article-title":"Clinically accurate diagnosis of Alzheimer\u2019s disease via multiplexed sensing of core biomarkers in human plasma","volume":"11","author":"Kim","year":"2020","journal-title":"Nat. Commun."},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"29","DOI":"10.1186\/s40580-020-00239-2","article-title":"Flexible nanopillar-based immunoelectrochemical biosensor for noninvasive detection of Amyloid beta","volume":"7","author":"Park","year":"2020","journal-title":"Nano Converg."},{"key":"ref_24","doi-asserted-by":"crossref","unstructured":"Park, D., Kim, J.H., Kim, H.J., Lee, D., Lee, D.S., Yoon, D.S., and Hwang, K.S. (2020). Multiplexed femtomolar detection of Alzheimer\u2019s disease biomarkers in biofluids using a reduced graphene oxide field-effect transistor. Biosens. Bioelectron., 167.","DOI":"10.1016\/j.bios.2020.112505"},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"7912","DOI":"10.1039\/D0RA00298D","article-title":"Electrochemical immunosensor based on AuBP@Pt nanostructure and AuPd-PDA nanozyme for ultrasensitive detection of APOE4","volume":"10","author":"Liu","year":"2020","journal-title":"RSC Adv."},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"5135","DOI":"10.1021\/acsnano.0c02823","article-title":"Rapid Detection of COVID-19 Causative Virus (SARS-CoV-2) in Human Nasopharyngeal Swab Specimens Using Field-Effect Transistor-Based Biosensor","volume":"14","author":"Seo","year":"2020","journal-title":"ACS Nano"},{"key":"ref_27","doi-asserted-by":"crossref","unstructured":"Yoo, Y.K., Kim, J., Kim, G., Kim, Y.S., Kim, H.Y., Lee, S., Cho, W.W., Kim, S., Lee, S.-M., and Lee, B.C. (2017). A highly sensitive plasma-based amyloid-\u03b2 detection system through medium-changing and noise cancellation system for early diagnosis of the Alzheimer\u2019s disease. Sci. Rep., 7.","DOI":"10.1038\/s41598-017-09370-3"},{"key":"ref_28","doi-asserted-by":"crossref","unstructured":"Razzino, C.A., Seraf\u00edn, V., Gamella, M., Pedrero, M., Montero-Calle, A., Barderas, R., Calero, M., Lobo, A.O., Y\u00e1\u00f1ez-Sede\u00f1o, P., and Campuzano, S. (2020). An electrochemical immunosensor using gold nanoparticles-PAMAM-nanostructured screen-printed carbon electrodes for tau protein determination in plasma and brain tissues from Alzheimer patients. Biosens. Bioelectron., 163.","DOI":"10.1016\/j.bios.2020.112238"},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"127710","DOI":"10.1016\/j.snb.2020.127710","article-title":"Gold nanoparticles assisted sensitivity improvement of interdigitated microelectrodes biosensor for amyloid-\u03b2 detection in plasma sample","volume":"308","author":"Yoo","year":"2020","journal-title":"Sens. Actuators B Chem."},{"key":"ref_30","first-page":"510","article-title":"Plasma amyloid beta levels are associated with cerebral amyloid and tau deposition","volume":"11","author":"Risacher","year":"2019","journal-title":"Alzheimer\u2019s Dement. Diagn. Assess. Dis. Monit."},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"197","DOI":"10.1016\/j.bios.2015.05.017","article-title":"Label-free detection of ApoE4-mediated \u03b2-amyloid aggregation on single nanoparticle uncovering Alzheimer\u2019s disease","volume":"72","author":"Kang","year":"2015","journal-title":"Biosens. Bioelectron."},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"141","DOI":"10.1016\/j.aca.2018.06.075","article-title":"Curcumin-graphene quantum dots for dual mode sensing platform: Electrochemical and fluorescence detection of APOe4, responsible of Alzheimer\u2019s disease","volume":"1036","author":"Mars","year":"2018","journal-title":"Anal. Chim. Acta"},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"1389","DOI":"10.1074\/mcp.M112.018861","article-title":"Total ApoE and ApoE4 isoform assays in an Alzheimer\u2019s disease case-control study by targeted mass spectrometry (n = 669): A pilot assay for methionine-containing proteotypic peptides","volume":"11","author":"Simon","year":"2012","journal-title":"Mol. Cell. Proteom."},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"181971","DOI":"10.1098\/rsos.181971","article-title":"Seedless gold nanostars with seed-like advantages for biosensing applications","volume":"6","author":"Phiri","year":"2019","journal-title":"R. Soc. Open Sci."},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"146031","DOI":"10.1155\/2013\/146031","article-title":"One-step synthesis of PEGylated gold nanoparticles with tunable surface charge","volume":"2013","author":"Stiufiuc","year":"2013","journal-title":"J. Nanomater."},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"282","DOI":"10.1016\/j.ijpharm.2019.02.012","article-title":"Chitosan and chitosan coating nanoparticles for the treatment of brain disease","volume":"560","author":"Yu","year":"2019","journal-title":"Int. J. Pharm."},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"2","DOI":"10.1038\/s41538-019-0034-z","article-title":"Chitosan-capped gold nanoparticles for indicating temperature abuse in frozen stored products","volume":"3","author":"Mohan","year":"2019","journal-title":"NPJ Sci. Food"},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"305","DOI":"10.1016\/j.bios.2017.07.014","article-title":"Portable amperometric immunosensor for histamine detection using Prussian blue-chitosan-gold nanoparticle nanocomposite films","volume":"98","author":"Dong","year":"2017","journal-title":"Biosens. Bioelectron."},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"45","DOI":"10.1016\/j.bios.2014.03.011","article-title":"A new signal amplification strategy of photoelectrochemical immunoassay for highly sensitive interleukin-6 detection based on TiO2\/CdS\/CdSe dual co-sensitized structure","volume":"59","author":"Fan","year":"2014","journal-title":"Biosens. Bioelectron."},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"1150","DOI":"10.1557\/s43579-023-00414-6","article-title":"Gold nanostar-modified electrochemical sensor for highly sensitive renin quantification as a marker of tissue-perfusion","volume":"13","author":"Schuck","year":"2023","journal-title":"MRS Commun."},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"97","DOI":"10.1007\/s40089-014-0097-4","article-title":"The study of synthesis and functionalized single-walled carbon nanotubes with amide group","volume":"4","author":"Abjameh","year":"2014","journal-title":"Int. Nano Lett."},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1016\/j.materresbull.2015.01.048","article-title":"Thionyl chloride assisted functionalization of amorphous carbon nanotubes: A better field emitter and stable nanofluid with better thermal conductivity","volume":"66","author":"Sarkar","year":"2015","journal-title":"Mater. Res. Bull."},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"2668","DOI":"10.1002\/pssb.201100106","article-title":"Effect of SOCl2 doping on electronic properties of single-walled carbon nanotube thin film transistors","volume":"248","author":"Kim","year":"2011","journal-title":"Phys. Status Solidi Basic Res."},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"83","DOI":"10.1016\/j.desal.2016.05.002","article-title":"Improvement in desalination performance of thin film nanocomposite nanofiltration membrane using amine-functionalized multiwalled carbon nanotube","volume":"394","author":"Zarrabi","year":"2016","journal-title":"Desalination"},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"443","DOI":"10.15671\/HJBC.2017.166","article-title":"Gold nanoparticle and poly(arginine) modified GCE for simultaneous determination of hydroquinone and catechol","volume":"3","year":"2017","journal-title":"Hacet. J. Biol. Chem."},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"274","DOI":"10.1007\/s13206-023-00102-6","article-title":"Comparison and Analysis of Polymer-Functionalized Carbon Nanotubes for Enhancement of the Quantitative Detection of Procalcitonin Levels in Human Plasma","volume":"17","author":"Schuck","year":"2023","journal-title":"BioChip J."}],"container-title":["Biosensors"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2079-6374\/14\/10\/510\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,10]],"date-time":"2025-10-10T16:15:38Z","timestamp":1760112938000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2079-6374\/14\/10\/510"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2024,10,17]]},"references-count":46,"journal-issue":{"issue":"10","published-online":{"date-parts":[[2024,10]]}},"alternative-id":["bios14100510"],"URL":"https:\/\/doi.org\/10.3390\/bios14100510","relation":{},"ISSN":["2079-6374"],"issn-type":[{"value":"2079-6374","type":"electronic"}],"subject":[],"published":{"date-parts":[[2024,10,17]]}}}