{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,5,13]],"date-time":"2026-05-13T02:09:02Z","timestamp":1778638142932,"version":"3.51.4"},"reference-count":204,"publisher":"MDPI AG","issue":"9","license":[{"start":{"date-parts":[[2020,4,30]],"date-time":"2020-04-30T00:00:00Z","timestamp":1588204800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100004543","name":"China Scholarship Council","doi-asserted-by":"publisher","award":["201707720041"],"award-info":[{"award-number":["201707720041"]}],"id":[{"id":"10.13039\/501100004543","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>To diagnose and treat early-stage (preclinical) Alzheimer\u2019s disease (AD) patients, we need body-fluid-based biomarkers that reflect the processes that occur in this stage, but current knowledge on associated processes is lacking. As human studies on (possible) onset and early-stage AD would be extremely expensive and time-consuming, we investigate the potential value of animal AD models to help to fill this knowledge gap. We provide a comprehensive overview of processes associated with AD pathogenesis and biomarkers, current knowledge on AD-related biomarkers derived from on human and animal brains and body fluids, comparisons of biomarkers obtained in human AD and frequently used animal AD models, and emerging body-fluid-based biomarkers. In human studies, amyloid beta (A\u03b2), hyperphosphorylated tau (P-tau), total tau (T-tau), neurogranin, SNAP-25, glial fibrillary acidic protein (GFAP), YKL-40, and especially neurofilament light (NfL) are frequently measured. In animal studies, the emphasis has been mostly on A\u03b2. Although a direct comparison between human (familial and sporadic) AD and (mostly genetic) animal AD models cannot be made, still, in brain, cerebrospinal fluid (CSF), and blood, a majority of similar trends are observed for human AD stage and animal AD model life stage. This indicates the potential value of animal AD models in understanding of the onset and early stage of AD. Moreover, animal studies can be smartly designed to provide mechanistic information on the interrelationships between the different AD processes in a longitudinal fashion and may also include the combinations of different conditions that may reflect comorbidities in human AD, according to the Mastermind Research approach.<\/jats:p>","DOI":"10.3390\/ijms21093158","type":"journal-article","created":{"date-parts":[[2020,5,4]],"date-time":"2020-05-04T14:00:43Z","timestamp":1588600843000},"page":"3158","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":21,"title":["Utility of Animal Models to Understand Human Alzheimer\u2019s Disease, Using the Mastermind Research Approach to Avoid Unnecessary Further Sacrifices of Animals"],"prefix":"10.3390","volume":"21","author":[{"given":"Tian","family":"Qin","sequence":"first","affiliation":[{"name":"Predictive Pharmacology, Division of Systems Biomedicine and Pharmacology, Leiden Academic Centre of Drug Research, Leiden University, 2333 CC Leiden, The Netherlands"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3882-7906","authenticated-orcid":false,"given":"Samantha","family":"Prins","sequence":"additional","affiliation":[{"name":"Centre for Human Drug Research (CHDR), 2333 CL Leiden, The Netherlands"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4655-6667","authenticated-orcid":false,"given":"Geert Jan","family":"Groeneveld","sequence":"additional","affiliation":[{"name":"Centre for Human Drug Research (CHDR), 2333 CL Leiden, The Netherlands"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0717-1817","authenticated-orcid":false,"given":"Gerard","family":"Van Westen","sequence":"additional","affiliation":[{"name":"Computational Drug Discovery, Division of Drug Discovery and Safety, Leiden Academic Centre of Drug Research, Leiden University, 2333 CC Leiden, The Netherlands"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7904-7124","authenticated-orcid":false,"given":"Helga E.","family":"de Vries","sequence":"additional","affiliation":[{"name":"Neuro-immunology research group, Department of Molecular Cell Biology and Immunology, Amsterdam Neuroscience, Amsterdam UMC, 1081 HZ Amsterdam, The Netherlands"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8577-3277","authenticated-orcid":false,"given":"Yin Cheong","family":"Wong","sequence":"additional","affiliation":[{"name":"Advanced Modelling and Simulation, UCB Celltech, Slough SL1 3WE, UK"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Luc J.M.","family":"Bischoff","sequence":"additional","affiliation":[{"name":"Predictive Pharmacology, Division of Systems Biomedicine and Pharmacology, Leiden Academic Centre of Drug Research, Leiden University, 2333 CC Leiden, The Netherlands"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8303-1117","authenticated-orcid":false,"given":"Elizabeth C.M.","family":"de Lange","sequence":"additional","affiliation":[{"name":"Predictive Pharmacology, Division of Systems Biomedicine and Pharmacology, Leiden Academic Centre of Drug Research, Leiden University, 2333 CC Leiden, The Netherlands"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2020,4,30]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"698","DOI":"10.1038\/nrd3505","article-title":"The amyloid cascade hypothesis for Alzheimer\u2019s disease: An appraisal for the development of therapeutics","volume":"10","author":"Karran","year":"2011","journal-title":"Nat. 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