{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,4,28]],"date-time":"2026-04-28T17:00:24Z","timestamp":1777395624017,"version":"3.51.4"},"reference-count":56,"publisher":"SAGE Publications","issue":"4","license":[{"start":{"date-parts":[[2019,7,12]],"date-time":"2019-07-12T00:00:00Z","timestamp":1562889600000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/journals.sagepub.com\/page\/policies\/text-and-data-mining-license"}],"content-domain":{"domain":["journals.sagepub.com"],"crossmark-restriction":true},"short-container-title":["Journal of Alzheimer\u2019s Disease"],"published-print":{"date-parts":[[2019,8,20]]},"abstract":"<jats:p>\u00a0Recent studies demonstrate that peripheral amylin treatment reduces pathology in mouse models of Alzheimer\u2019s disease (AD). However, soluble and aggregated amylin are distinct species; while amylin is a physiological neuropeptide, amylin aggregation is a pathological factor for diabetes. We thus hypothesized that because of their similarity in secondary structures, amylin antagonizes amyloid-\u03b2 peptide (A\u03b2)-induced AD pathology in neurons with a dose-dependent pattern. To test the hypothesis, we conducted both in vitro and in vivo experiments with different doses of amylin and with its analog, pramlintide. Here we report that a high concentration of either A\u03b2 or amylin alone induced tau phosphorylation (pTau) in primary neurons. Interestingly, with a low concentration, amylin had direct effects to reverse the A\u03b2-induced pTau, as well as damaged neuronal synapses and neurite disorganization. However, when the concentration was high (10.24 \u03bcM), amylin lost the effects against the A\u03b2-induced cellular AD pathology and, together with A\u03b2, worsened tauopathy in neurons. In the 5XFAD AD mouse model, daily peripheral amylin treatment with a low dose (200 \u03bcg\/kg) more effectively reduced amyloid burden, and increased synapse, but with a high dose (800 \u03bcg\/kg), it more effectively reduced tauopathy. Correspondingly, amylin treatment improved learning and memory in these mice. It demonstrates that amylin has a dose-dependent U-shape effect against AD pathogenesis. Within a physiological range, amylin is a neuroprotective hormone against AD in neurons; but when both A\u03b2 and amylin concentrations are elevated, imbalance of A\u03b2 and amylin may contribute to brain AD pathogenesis.<\/jats:p>","DOI":"10.3233\/jad-190161","type":"journal-article","created":{"date-parts":[[2019,7,12]],"date-time":"2019-07-12T14:01:25Z","timestamp":1562940085000},"page":"1025-1040","update-policy":"https:\/\/doi.org\/10.1177\/sage-journals-update-policy","source":"Crossref","is-referenced-by-count":8,"title":["Effects of Amylin Against Amyloid-\u03b2-Induced Tauopathy and Synapse Loss in Primary Neurons"],"prefix":"10.1177","volume":"70","author":[{"given":"Qini","family":"Gan","sequence":"first","affiliation":[{"name":"Department of Pharmacology and Experimental Therapeutics, Boston University School of Medicine, Boston, MA, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Hongbo","family":"Yao","sequence":"additional","affiliation":[{"name":"Department of Pharmacology and Experimental Therapeutics, Boston University School of Medicine, Boston, MA, USA"},{"name":"Department of Histology and Embriology, Qiqihaer Medical University, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Hana","family":"Na","sequence":"additional","affiliation":[{"name":"Department of Pharmacology and Experimental Therapeutics, Boston University School of Medicine, Boston, MA, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Heather","family":"Ballance","sequence":"additional","affiliation":[{"name":"Department of Pharmacology and Experimental Therapeutics, Boston University School of Medicine, Boston, MA, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Qiushan","family":"Tao","sequence":"additional","affiliation":[{"name":"Department of Pharmacology and Experimental Therapeutics, Boston University School of Medicine, Boston, MA, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Lorene","family":"Leung","sequence":"additional","affiliation":[{"name":"Department of Pharmacology and Experimental Therapeutics, Boston University School of Medicine, Boston, MA, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Hua","family":"Tian","sequence":"additional","affiliation":[{"name":"Department of Pharmacology and Experimental Therapeutics, Boston University School of Medicine, Boston, MA, USA"},{"name":"Department of Histology and Embriology, Qiqihaer Medical University, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Haihao","family":"Zhu","sequence":"additional","affiliation":[{"name":"Department of Pharmacology and Experimental Therapeutics, Boston University School of Medicine, Boston, MA, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Benjamin","family":"Wolozin","sequence":"additional","affiliation":[{"name":"Department of Pharmacology and Experimental Therapeutics, Boston University School of Medicine, Boston, MA, USA"},{"name":"Department of Neurology, Boston University School of Medicine, Boston, MA, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Wei Qiao","family":"Qiu","sequence":"additional","affiliation":[{"name":"Department of Pharmacology and Experimental Therapeutics, Boston University School of Medicine, Boston, MA, USA"},{"name":"Alzheimer\u2019s Disease Center, Boston University School of Medicine, Boston, MA, USA"},{"name":"Department of Psychiatry, Boston University School of Medicine, Boston, MA, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"179","published-online":{"date-parts":[[2019,7,12]]},"reference":[{"key":"ref001","doi-asserted-by":"publisher","DOI":"10.1210\/mend-3-11-1775"},{"key":"ref002","doi-asserted-by":"publisher","DOI":"10.1111\/j.1463-1326.2012.01670.x"},{"key":"ref003","doi-asserted-by":"publisher","DOI":"10.1016\/j.physbeh.2016.02.034"},{"key":"ref004","doi-asserted-by":"publisher","DOI":"10.3389\/fnagi.2014.00186"},{"key":"ref005","doi-asserted-by":"publisher","DOI":"10.1016\/j.neurobiolaging.2013.10.076"},{"key":"ref006","doi-asserted-by":"publisher","DOI":"10.1038\/mp.2016.35"},{"key":"ref007","doi-asserted-by":"publisher","DOI":"10.1126\/science.1072994"},{"key":"ref008","doi-asserted-by":"publisher","DOI":"10.1016\/j.febslet.2008.05.006"},{"key":"ref009","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M111.331181"},{"key":"ref010","doi-asserted-by":"publisher","DOI":"10.1210\/en.2013-1658"},{"key":"ref011","doi-asserted-by":"publisher","DOI":"10.1038\/mp.2014.17"},{"key":"ref012","doi-asserted-by":"publisher","DOI":"10.1016\/j.neuropharm.2017.03.030"},{"key":"ref013","doi-asserted-by":"publisher","DOI":"10.1111\/j.1471-4159.1993.tb07480.x"},{"key":"ref014","doi-asserted-by":"publisher","DOI":"10.1038\/368756a0"},{"key":"ref015","doi-asserted-by":"publisher","DOI":"10.1002\/ana.23956"},{"key":"ref016","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M201750200"},{"key":"ref017","doi-asserted-by":"publisher","DOI":"10.1523\/JNEUROSCI.1202-06.2006"},{"key":"ref018","doi-asserted-by":"publisher","DOI":"10.1038\/nprot.2012.099"},{"key":"ref019","doi-asserted-by":"publisher","DOI":"10.1523\/JNEUROSCI.19-07-02455.1999"},{"key":"ref020","doi-asserted-by":"publisher","DOI":"10.1038\/srep07608"},{"key":"ref021","doi-asserted-by":"publisher","DOI":"10.1002\/jnr.23193"},{"key":"ref022","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.87.15.5827"},{"key":"ref023","doi-asserted-by":"publisher","DOI":"10.1016\/S0021-9258(18)41890-X"},{"key":"ref024","doi-asserted-by":"publisher","DOI":"10.1038\/78078"},{"key":"ref025","doi-asserted-by":"publisher","DOI":"10.1002\/ar.22641"},{"key":"ref026","doi-asserted-by":"publisher","DOI":"10.1002\/ar.22688"},{"key":"ref027","doi-asserted-by":"publisher","DOI":"10.1038\/35050110"},{"key":"ref028","doi-asserted-by":"publisher","DOI":"10.1242\/dev.119.4.1029"},{"key":"ref029","doi-asserted-by":"publisher","DOI":"10.1016\/0014-5793(93)80849-P"},{"key":"ref030","doi-asserted-by":"publisher","DOI":"10.1038\/371419a0"},{"key":"ref031","doi-asserted-by":"publisher","DOI":"10.1007\/s001250051364"},{"key":"ref032","doi-asserted-by":"publisher","DOI":"10.1016\/j.neuropharm.2016.07.008"},{"key":"ref033","doi-asserted-by":"publisher","DOI":"10.1016\/j.neuroscience.2010.10.008"},{"key":"ref034","doi-asserted-by":"publisher","DOI":"10.1159\/000430199"},{"key":"ref035","doi-asserted-by":"publisher","DOI":"10.1016\/j.neuroscience.2017.05.024"},{"key":"ref036","doi-asserted-by":"publisher","DOI":"10.2337\/db07-0849"},{"key":"ref037","doi-asserted-by":"publisher","DOI":"10.1016\/j.neurobiolaging.2014.06.015"},{"key":"ref038","doi-asserted-by":"publisher","DOI":"10.1002\/jnr.22227"},{"key":"ref039","doi-asserted-by":"publisher","DOI":"10.1016\/j.neurobiolaging.2005.04.008"},{"key":"ref040","doi-asserted-by":"publisher","DOI":"10.1093\/brain\/awu046"},{"key":"ref041","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M112.401240"},{"key":"ref042","doi-asserted-by":"publisher","DOI":"10.1006\/bbrc.1998.9308"},{"key":"ref043","doi-asserted-by":"publisher","DOI":"10.1124\/pr.115.010629"},{"key":"ref044","doi-asserted-by":"publisher","DOI":"10.1016\/S0026-895X(24)08983-1"},{"key":"ref045","doi-asserted-by":"publisher","DOI":"10.1111\/head.13077"},{"key":"ref046","doi-asserted-by":"publisher","DOI":"10.1111\/j.1476-5381.2011.01537.x"},{"key":"ref047","doi-asserted-by":"publisher","DOI":"10.1021\/bi981658g"},{"key":"ref048","doi-asserted-by":"publisher","DOI":"10.1111\/j.1463-1326.2010.01201.x"},{"key":"ref049","doi-asserted-by":"publisher","DOI":"10.1055\/s-2007-978867"},{"key":"ref050","doi-asserted-by":"publisher","DOI":"10.1007\/s10495-011-0656-3"},{"key":"ref051","doi-asserted-by":"publisher","DOI":"10.1002\/j.1552-4604.1996.tb04147.x"},{"key":"ref052","doi-asserted-by":"publisher","DOI":"10.1016\/S1054-3589(05)52017-9"},{"key":"ref053","doi-asserted-by":"publisher","DOI":"10.1002\/anie.200904902"},{"key":"ref054","doi-asserted-by":"publisher","DOI":"10.1002\/anie.201105877"},{"key":"ref055","doi-asserted-by":"publisher","DOI":"10.1002\/anie.200604056"},{"key":"ref056","doi-asserted-by":"publisher","DOI":"10.2174\/13816128113199990064"}],"container-title":["Journal of Alzheimer\u2019s Disease"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/journals.sagepub.com\/doi\/pdf\/10.3233\/JAD-190161","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/journals.sagepub.com\/doi\/full-xml\/10.3233\/JAD-190161","content-type":"application\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/journals.sagepub.com\/doi\/pdf\/10.3233\/JAD-190161","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,4,28]],"date-time":"2026-04-28T10:06:16Z","timestamp":1777370776000},"score":1,"resource":{"primary":{"URL":"https:\/\/journals.sagepub.com\/doi\/10.3233\/JAD-190161"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2019,7,12]]},"references-count":56,"journal-issue":{"issue":"4","published-print":{"date-parts":[[2019,8,20]]}},"alternative-id":["10.3233\/JAD-190161"],"URL":"https:\/\/doi.org\/10.3233\/jad-190161","relation":{},"ISSN":["1387-2877","1875-8908"],"issn-type":[{"value":"1387-2877","type":"print"},{"value":"1875-8908","type":"electronic"}],"subject":[],"published":{"date-parts":[[2019,7,12]]}}}