{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,4,28]],"date-time":"2026-04-28T16:05:35Z","timestamp":1777392335416,"version":"3.51.4"},"reference-count":84,"publisher":"SAGE Publications","issue":"1","license":[{"start":{"date-parts":[[2019,7,2]],"date-time":"2019-07-02T00:00:00Z","timestamp":1562025600000},"content-version":"unspecified","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by-nc\/4.0\/"}],"content-domain":{"domain":["journals.sagepub.com"],"crossmark-restriction":true},"short-container-title":["Journal of Alzheimer's Disease Reports"],"published-print":{"date-parts":[[2019,7,2]]},"abstract":"<jats:p>A five-year close reading of the scientific literature on late-onset Alzheimer\u2019s disease (AD) has prompted the invention of a novel therapeutic method that biomechanistically targets the targetable disease-process targets of AD with one or another mixture of non-toxic pleiotropic natural compounds. The featured mixture herein is comprised of curcumin, resveratrol, and EGCG. The mixture\u2019s targets include central pathological elements of AD (including amyloid, tau, synaptic dysfunction, oxidative stress, mitochondrial dysfunction, and aberrant neuroinflammation), modifiable risk factors, comorbidities, and epigenetic elements. The featured mixture and other such mixtures are suitable for long-term use, and may be applied to any stage of AD, including primary and secondary prevention. Such mixtures also would be amenable for use as pre-treatment, co-treatment, and post-treatment applications with certain biopharmaceutical agents. The targeting focus here is the major credible hypotheses of AD. The focus of future such articles will include other AD-related targets, modifiable risk factors and comorbidities, APOE4, epigenetic factors, bioavailability, dose response, and implications for clinical testing. The \u201cuniversal targeting\u201d method described herein\u2014that is, \u201ctargeting the targetable targets\u201d of AD using certain mixtures of natural compounds\u2014is reprogrammable and thus is applicable to other chronic neurological conditions, including Parkinson\u2019s disease, vascular dementia, ischemic-stroke prevention and recovery, and sports-related head injuries and sequelae leading to chronic traumatic encephalopathy.<\/jats:p>","DOI":"10.3233\/adr-190127","type":"journal-article","created":{"date-parts":[[2019,7,26]],"date-time":"2019-07-26T12:26:45Z","timestamp":1564144005000},"page":"219-232","update-policy":"https:\/\/doi.org\/10.1177\/sage-journals-update-policy","source":"Crossref","is-referenced-by-count":2,"title":["Biopharmaceutical Monotargeting versus \u2018Universal Targeting\u2019 of Late-Onset Alzheimer\u2019s Disease Using Mixtures of Pleiotropic Natural Compounds"],"prefix":"10.1177","volume":"3","author":[{"given":"Howard","family":"Friel","sequence":"first","affiliation":[{"name":"Universal Targeting, Northampton, MA, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"179","published-online":{"date-parts":[[2019,7,24]]},"reference":[{"key":"ref001","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M600617200"},{"key":"ref002","doi-asserted-by":"publisher","DOI":"10.3945\/jn.109.109785"},{"key":"ref003","doi-asserted-by":"publisher","DOI":"10.1096\/fj.02-0881fje"},{"key":"ref004","doi-asserted-by":"publisher","DOI":"10.1016\/j.neulet.2010.01.026"},{"key":"ref005","doi-asserted-by":"publisher","DOI":"10.1016\/j.bbrc.2012.07.010"},{"key":"ref006","doi-asserted-by":"publisher","DOI":"10.1016\/j.neulet.2010.08.035"},{"key":"ref007","doi-asserted-by":"publisher","DOI":"10.1186\/1472-6882-14-88"},{"key":"ref008","doi-asserted-by":"publisher","DOI":"10.1007\/s11418-014-0859-3"},{"key":"ref009","doi-asserted-by":"publisher","DOI":"10.1016\/S1734-1140(11)70629-6"},{"key":"ref010","doi-asserted-by":"publisher","DOI":"10.3892\/etm.2011.246"},{"key":"ref011","doi-asserted-by":"publisher","DOI":"10.1016\/j.bmcl.2011.12.034"},{"key":"ref012","doi-asserted-by":"publisher","DOI":"10.1097\/WNR.0b013e32830b8ae1"},{"key":"ref013","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa1210951"},{"key":"ref014","doi-asserted-by":"publisher","DOI":"10.1021\/cn200088r"},{"key":"ref015","doi-asserted-by":"publisher","DOI":"10.1111\/cbdd.12552"},{"key":"ref016","doi-asserted-by":"publisher","DOI":"10.1111\/j.1460-9568.2005.04532.x"},{"key":"ref017","doi-asserted-by":"publisher","DOI":"10.1016\/j.phymed.2010.03.008"},{"key":"ref018","doi-asserted-by":"publisher","DOI":"10.1016\/j.nano.2011.06.015"},{"key":"ref019","doi-asserted-by":"publisher","DOI":"10.1021\/jp202640b"},{"key":"ref020","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M404751200"},{"key":"ref021","doi-asserted-by":"publisher","DOI":"10.1016\/j.neuint.2008.10.008"},{"key":"ref022","doi-asserted-by":"publisher","DOI":"10.1111\/j.1471-4159.2007.04613.x"},{"key":"ref023","doi-asserted-by":"publisher","DOI":"10.1007\/978-3-319-08927-0_12"},{"key":"ref024","doi-asserted-by":"publisher","DOI":"10.1016\/j.neuroscience.2017.08.030"},{"key":"ref025","doi-asserted-by":"publisher","DOI":"10.3233\/JAD-2006-10101"},{"key":"ref026","doi-asserted-by":"publisher","DOI":"10.18632\/oncotarget.24369"},{"key":"ref027","doi-asserted-by":"publisher","DOI":"10.1007\/s11064-012-0754-9"},{"key":"ref028","doi-asserted-by":"publisher","DOI":"10.1021\/acschemneuro.5b00214"},{"key":"ref029","doi-asserted-by":"publisher","DOI":"10.4062\/biomolther.2019.046"},{"key":"ref030","doi-asserted-by":"publisher","DOI":"10.18632\/oncotarget.6863"},{"key":"ref031","doi-asserted-by":"publisher","DOI":"10.1016\/j.pharmthera.2012.07.001"},{"key":"ref032","unstructured":"PunskyK (2015) Mayo Clinic Study of Thousands of Brains Reveals Tau as Driver of Alzheimer\u2019s Disease, Mayo Clinic News Network, https:\/\/newsnetwork.mayoclinic.org\/discussion\/mayo-clinic-study-of-thousands-of-brains-reveals-tau-as-driver-of-alzheimers-disease\/ Posted March 23, 2015. Last accessed 16 June 2019."},{"key":"ref033","doi-asserted-by":"publisher","DOI":"10.2174\/092986708785909111"},{"key":"ref034","doi-asserted-by":"publisher","DOI":"10.2174\/156720511796717177"},{"key":"ref035","doi-asserted-by":"publisher","DOI":"10.1517\/14728222.2014.870156"},{"key":"ref036","doi-asserted-by":"publisher","DOI":"10.1016\/j.fct.2008.05.030"},{"key":"ref037","doi-asserted-by":"publisher","DOI":"10.3233\/JAD-170351"},{"key":"ref038","doi-asserted-by":"publisher","DOI":"10.1016\/j.febslet.2014.11.026"},{"key":"ref039","doi-asserted-by":"publisher","DOI":"10.3389\/fnagi.2018.00244"},{"key":"ref040","doi-asserted-by":"publisher","DOI":"10.1007\/s11357-012-9489-4"},{"key":"ref041","doi-asserted-by":"publisher","DOI":"10.3389\/fnins.2016.00598"},{"key":"ref042","doi-asserted-by":"publisher","DOI":"10.1126\/science.1074069"},{"key":"ref043","doi-asserted-by":"publisher","DOI":"10.1038\/nm1782"},{"key":"ref044","doi-asserted-by":"publisher","DOI":"10.1016\/j.neuron.2014.05.004"},{"key":"ref045","doi-asserted-by":"publisher","DOI":"10.1515\/tnsci-2015-0023"},{"key":"ref046","doi-asserted-by":"publisher","DOI":"10.1111\/ejn.12504"},{"key":"ref047","doi-asserted-by":"publisher","DOI":"10.1177\/0394632016638099"},{"key":"ref048","doi-asserted-by":"publisher","DOI":"10.1016\/j.tiv.2013.10.002"},{"key":"ref049","doi-asserted-by":"publisher","DOI":"10.1007\/978-3-319-18365-7_4"},{"key":"ref050","doi-asserted-by":"publisher","DOI":"10.1016\/j.neuroscience.2016.08.051"},{"key":"ref051","doi-asserted-by":"publisher","DOI":"10.1016\/j.neuroscience.2009.07.014"},{"key":"ref052","first-page":"82323","volume":"3","author":"Nunomura A","year":"2006","journal-title":"J Biomed Biotechnol"},{"key":"ref053","doi-asserted-by":"publisher","DOI":"10.1007\/s12640-012-9331-x"},{"key":"ref054","doi-asserted-by":"publisher","DOI":"10.1089\/ars.2012.5039"},{"key":"ref055","doi-asserted-by":"publisher","DOI":"10.2174\/09298673113209990152"},{"key":"ref056","doi-asserted-by":"publisher","DOI":"10.1155\/2014\/497802"},{"key":"ref057","doi-asserted-by":"publisher","DOI":"10.4103\/1673-5374.153700"},{"key":"ref058","doi-asserted-by":"publisher","DOI":"10.1016\/j.exger.2013.07.002"},{"key":"ref059","doi-asserted-by":"publisher","DOI":"10.3109\/10799893.2015.1108337"},{"key":"ref060","doi-asserted-by":"publisher","DOI":"10.1016\/j.toxlet.2017.10.021"},{"key":"ref061","doi-asserted-by":"publisher","DOI":"10.1007\/s11064-017-2421-7"},{"key":"ref062","doi-asserted-by":"publisher","DOI":"10.2174\/187152710791012071"},{"key":"ref063","doi-asserted-by":"publisher","DOI":"10.1517\/14728222.2014.988707"},{"key":"ref064","doi-asserted-by":"publisher","DOI":"10.1016\/bs.apcsb.2017.02.001"},{"key":"ref065","doi-asserted-by":"publisher","DOI":"10.1016\/S1474-4422(15)70016-5"},{"key":"ref066","doi-asserted-by":"publisher","DOI":"10.3109\/00207454.2013.833510"},{"key":"ref067","doi-asserted-by":"publisher","DOI":"10.3389\/fphar.2016.00261"},{"key":"ref068","doi-asserted-by":"publisher","DOI":"10.1016\/j.neulet.2015.03.045"},{"key":"ref069","doi-asserted-by":"publisher","DOI":"10.1016\/j.ejphar.2015.11.048"},{"key":"ref070","doi-asserted-by":"publisher","DOI":"10.1016\/j.jnutbio.2012.06.011"},{"key":"ref071","doi-asserted-by":"publisher","DOI":"10.3892\/mmr.2015.4199"},{"key":"ref072","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M509329200"},{"key":"ref073","doi-asserted-by":"publisher","DOI":"10.1155\/2017\/9302761"},{"key":"ref074","doi-asserted-by":"publisher","DOI":"10.1016\/j.freeradbiomed.2017.08.021"},{"key":"ref075","doi-asserted-by":"publisher","DOI":"10.1016\/bs.pmbts.2016.12.019"},{"key":"ref076","doi-asserted-by":"publisher","DOI":"10.1007\/s12035-015-9515-5"},{"key":"ref077","doi-asserted-by":"publisher","DOI":"10.3233\/JAD-160726"},{"key":"ref078","doi-asserted-by":"publisher","DOI":"10.3233\/JAD-160702"},{"key":"ref079","doi-asserted-by":"publisher","DOI":"10.1016\/j.freeradbiomed.2015.05.041"},{"key":"ref080","doi-asserted-by":"publisher","DOI":"10.1016\/j.neuint.2013.02.014"},{"key":"ref081","doi-asserted-by":"publisher","DOI":"10.1136\/jim-2016-000240"},{"key":"ref082","doi-asserted-by":"publisher","DOI":"10.3233\/JAD-2011-101629"},{"key":"ref083","doi-asserted-by":"publisher","DOI":"10.1007\/s12035-016-9770-0"},{"key":"ref084","doi-asserted-by":"publisher","DOI":"10.1007\/s12035-017-0448-z"}],"container-title":["Journal of Alzheimer's Disease Reports"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/journals.sagepub.com\/doi\/pdf\/10.3233\/ADR-190127","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/journals.sagepub.com\/doi\/full-xml\/10.3233\/ADR-190127","content-type":"application\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/journals.sagepub.com\/doi\/pdf\/10.3233\/ADR-190127","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,4,28]],"date-time":"2026-04-28T09:56:42Z","timestamp":1777370202000},"score":1,"resource":{"primary":{"URL":"https:\/\/journals.sagepub.com\/doi\/10.3233\/ADR-190127"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2019,7,2]]},"references-count":84,"journal-issue":{"issue":"1","published-print":{"date-parts":[[2019,7,2]]}},"alternative-id":["10.3233\/ADR-190127"],"URL":"https:\/\/doi.org\/10.3233\/adr-190127","relation":{},"ISSN":["2542-4823","2542-4823"],"issn-type":[{"value":"2542-4823","type":"print"},{"value":"2542-4823","type":"electronic"}],"subject":[],"published":{"date-parts":[[2019,7,2]]}}}