{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,11]],"date-time":"2026-06-11T14:34:13Z","timestamp":1781188453278,"version":"3.54.1"},"reference-count":16,"publisher":"Wiley","issue":"1","license":[{"start":{"date-parts":[[2019,3,14]],"date-time":"2019-03-14T00:00:00Z","timestamp":1552521600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"}],"content-domain":{"domain":["alz-journals.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Alz &amp;amp; Dem Diag Ass &amp;amp; Dis Mo"],"published-print":{"date-parts":[[2019,12]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:p>For decades, scientists have known that carriers of the apolipoprotein E \u03b54 (<jats:italic>APOE<\/jats:italic> \u03b54) allele (homozygous\/heterozygous) are at respectively higher risk for developing Alzheimer's disease (AD). Although previous research reveals that the <jats:italic>APOE<\/jats:italic> \u03b54 variant impacts the clearance capacity and degradation of \u03b2\u2010amyloid from the brain, as compared with <jats:italic>APOE<\/jats:italic> \u03b53 (wild type with normal risk) and <jats:italic>APOE<\/jats:italic> \u03b52 (variant with accelerated clearance and reduced risk), little has been documented about <jats:italic>APOE<\/jats:italic> \u03b54's dual role in cholesterol transport, both peripheral and cerebral, and the effects of sluggish <jats:italic>APOE<\/jats:italic> \u03b54 cholesterol transport on cerebral metabolic rate. An understanding of the connection between brain metabolism and brain fat\/cholesterol transport may unlock new prevention strategies for treating patients with a comorbidity of metabolic syndrome (MetS) with cognitive impairment. Recent findings suggest that the <jats:italic>APOE<\/jats:italic> \u03b54 carrier impedes the shuttling of lipids from neurons and circumvents the storage of fat within the glia lipid droplets. This sluggish transport of lipids to triglyceride droplets in the glia cells can lead to dangerous reactive oxygen species and hydroxyl\u2010free radicals as lipids are prematurely oxidized.<\/jats:p><jats:p>This case study evaluates the effects of a 10\u2010week clinically prescribed ketogenic diet (KD) with a 68\u2010year\u2010old male, heterozygous <jats:italic>APOE<\/jats:italic> \u03b54 carrier, with a dual diagnosis of mild AD and type 2 diabetes (T2DM). The patient was administering both long\u2010 and short\u2010acting injectable insulin to mediate his T2DM for 15+ years. Clinical goals of the intervention included increased hypothalamic and peripheral insulin sensitivity as measured via blood ketones with the Abbott Precision Xtra Blood Ketone Meter to confirm metabolic flexibility; controlled plasma glucose as measured via Abbott Precision Xtra Blood Glucose Meter and HgA1c via venous draw; normalization of lipid panel via venous draw and improved memory with restoration of cognitive functionality measured via the Montreal Cognitive Assessment. The Montreal Cognitive Assessment is considered to be a gold standard assessment in the diagnosis of early AD. Physiological biomarkers for T2DM\/MetS and cognitive functionality were assessed before\/during\/after intervention. These measures included HOMA\u2010IR, triglycerides\/HDL ratio, HgA1c, fasting glucose, fasting insulin, complete fasting lipid panel and the PEAK mobile application for real\u2010time measurement of cognitive improvement. The results were statistically significant. The patient's baseline Montreal Cognitive Assessment improved from 23\/30 (mild AD) to 29\/30 (normal \u2265 26). His T2DM was reversed. Pre\u2010intervention HgA1c was 7.8% (T2DM); post intervention HgA1c measured 5.5% (normal). Likewise, the patient achieved statistically significant improvements in the other aforementioned biomarkers of MetS. The results of this case study suggest that a clinically prescribed ketogenic diet has strong potential to restore systemic insulin sensitivity and metabolic flexibility in diabetic, <jats:italic>APOE<\/jats:italic> \u03b54 heterozygous carriers. Mechanisms of action point to normalization of homeostatic negative feedback loops resetting\/restoring lipid synthesis\/utilization and glucose (insulin)\/fatty acid (glucagon) utilization\/production in both the body and brain, resulting in increased cerebral metabolism, improved cognition, and reversal of T2DM via renewed cellular insulin sensitivity.<\/jats:p>","DOI":"10.1016\/j.dadm.2019.01.009","type":"journal-article","created":{"date-parts":[[2019,3,14]],"date-time":"2019-03-14T00:05:56Z","timestamp":1552521956000},"page":"264-269","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":14,"title":["<i>APOE<\/i> \u03b54, the door to insulin\u2010resistant dyslipidemia and brain fog? A case study"],"prefix":"10.1002","volume":"11","author":[{"given":"Seth","family":"Stoykovich","sequence":"first","affiliation":[{"name":"Bethel University St. Paul MN USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kelly","family":"Gibas","sequence":"additional","affiliation":[{"name":"Bethel University St. Paul MN USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2019,3,14]]},"reference":[{"key":"e_1_2_9_2_2","article-title":"Late\u2010onset Alzheimer's disease is associated with inherent changes in bioenergetics profiles","volume":"7","author":"Sonntag K.","year":"2017","journal-title":"Scientific Rep"},{"key":"e_1_2_9_3_2","doi-asserted-by":"publisher","DOI":"10.3389\/fnins.2018.00830"},{"key":"e_1_2_9_4_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.neuron.2014.08.005"},{"key":"e_1_2_9_5_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.neuint.2017.09.004"},{"key":"e_1_2_9_6_2","doi-asserted-by":"crossref","first-page":"26119","DOI":"10.1038\/srep26119","article-title":"ApoE4 expression accelerates hippocampus\u2010dependent cognitive deficits by enhancing A impairment of insulin signaling in an Alzheimer's disease mouse model","volume":"6","author":"Chan E.S.","year":"2016","journal-title":"Sci Rep"},{"key":"e_1_2_9_7_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.neuron.2017.09.003"},{"key":"e_1_2_9_8_2","doi-asserted-by":"publisher","DOI":"10.1111\/jnc.13107"},{"key":"e_1_2_9_9_2","doi-asserted-by":"publisher","DOI":"10.3389\/fphys.2014.00522"},{"key":"e_1_2_9_10_2","doi-asserted-by":"publisher","DOI":"10.1111\/nyas.12999"},{"key":"e_1_2_9_11_2","doi-asserted-by":"publisher","DOI":"10.1097\/WAD.0b013e3182420bfe"},{"key":"e_1_2_9_12_2","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.97.10.5440"},{"key":"e_1_2_9_13_2","doi-asserted-by":"crossref","DOI":"10.1016\/j.dsx.2017.03.022","article-title":"Induced and controlled dietary ketosis as a regulator of obesity and metabolic syndrome pathologies","volume":"11","author":"Gibas M.K.","year":"2017","journal-title":"Diabetes Metab Syndr Clin Res Rev"},{"key":"e_1_2_9_14_2","doi-asserted-by":"publisher","DOI":"10.1186\/1743-7075-6-31"},{"key":"e_1_2_9_15_2","volume-title":"Testing the validity of the PEAK relational training system in assessing language & cognition after brain injury","author":"Whiteford K.M.","year":"2014"},{"key":"e_1_2_9_16_2","doi-asserted-by":"publisher","DOI":"10.1136\/bmj.k4925"},{"key":"e_1_2_9_17_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.fshw.2016.10.003"}],"container-title":["Alzheimer's &amp; Dementia: Diagnosis, Assessment &amp; Disease Monitoring"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/api.elsevier.com\/content\/article\/PII:S2352872919300120?httpAccept=text\/xml","content-type":"text\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/api.elsevier.com\/content\/article\/PII:S2352872919300120?httpAccept=text\/plain","content-type":"text\/plain","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/api.wiley.com\/onlinelibrary\/tdm\/v1\/articles\/10.1016%2Fj.dadm.2019.01.009","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1016\/j.dadm.2019.01.009","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/full-xml\/10.1016\/j.dadm.2019.01.009","content-type":"application\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/alz-journals.onlinelibrary.wiley.com\/doi\/pdf\/10.1016\/j.dadm.2019.01.009","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,14]],"date-time":"2025-10-14T11:41:51Z","timestamp":1760442111000},"score":1,"resource":{"primary":{"URL":"https:\/\/alz-journals.onlinelibrary.wiley.com\/doi\/10.1016\/j.dadm.2019.01.009"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2019,3,14]]},"references-count":16,"journal-issue":{"issue":"1","published-print":{"date-parts":[[2019,12]]}},"alternative-id":["10.1016\/j.dadm.2019.01.009"],"URL":"https:\/\/doi.org\/10.1016\/j.dadm.2019.01.009","archive":["Portico"],"relation":{},"ISSN":["2352-8729","2352-8729"],"issn-type":[{"value":"2352-8729","type":"print"},{"value":"2352-8729","type":"electronic"}],"subject":[],"published":{"date-parts":[[2019,3,14]]},"assertion":[{"value":"2019-03-14","order":3,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}]}}