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In elderly subjects with cognitive decline, supplementation with folate, cobalamin, and pyridoxal demonstrated reduction of cerebral atrophy in gray matter regions vulnerable to the AD process. Multiple pathogenic microbes are implicated as pathogenic factors in AD and atherosclerosis, and the deposition of amyloid-\u03b2 (A\u03b2), phosphorylation of tau protein, neuronal injury, and apoptosis in AD are secondary to microbial infection. Glucose utilization and blood flow are reduced in AD, and these changes are accompanied by downregulation of glucose transport, Na, K-ATPase, oxidative phosphorylation, and energy consumption. Thioretinaco ozonide, the complex formed from thioretinamide, cobalamin, ozone, and oxygen is proposed to constitute the active site of oxidative phosphorylation, catalyzing synthesis of adenosine triphosphate (ATP) from nicotinamide adenine dinucleotide (NAD\n                    <jats:sup>+<\/jats:sup>\n                    ) and phosphate. Pathogenic microbes cause synthesis of polyamines in host cells by increasing the transfer of aminopropyl groups from adenosyl methionine to putrescine, resulting in depletion of intracellular adenosyl methionine concentrations in host cells. Depletion of adenosyl methionine causes dysregulation of methionine metabolism, hyperhomocysteinemia, reduced biosynthesis of thioretinamide and thioretinaco ozonide, decreased oxidative phosphorylation, decreased production of nitric oxide and peroxynitrite, and impaired host response to infectious microbes, contributing to the pathogenesis of dementia and atherosclerosis.\n                  <\/jats:p>","DOI":"10.3233\/jad-160549","type":"journal-article","created":{"date-parts":[[2016,8,16]],"date-time":"2016-08-16T14:37:27Z","timestamp":1471358247000},"page":"1283-1290","update-policy":"https:\/\/doi.org\/10.1177\/sage-journals-update-policy","source":"Crossref","is-referenced-by-count":16,"title":["Homocysteine, Infections, Polyamines, Oxidative Metabolism, and the Pathogenesis of Dementia and Atherosclerosis"],"prefix":"10.1177","volume":"54","author":[{"given":"Kilmer S.","family":"McCully","sequence":"first","affiliation":[{"name":"The Pathology and Laboratory Medicine Service, VA Boston Healthcare System, Harvard Medical School, Boston, MA, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"179","published-online":{"date-parts":[[2016,8,10]]},"reference":[{"key":"e_1_3_1_2_2","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa011613"},{"key":"e_1_3_1_3_2","doi-asserted-by":"publisher","DOI":"10.1001\/archneur.55.11.1449"},{"key":"e_1_3_1_4_2","doi-asserted-by":"publisher","DOI":"10.1002\/(SICI)1099-1166(199804)13:4<235::AID-GPS761>3.0.CO;2-8"},{"key":"e_1_3_1_5_2","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.1301816110"},{"key":"e_1_3_1_6_2","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa1504327"},{"key":"e_1_3_1_7_2","doi-asserted-by":"publisher","DOI":"10.3233\/JAD-160152"},{"key":"e_1_3_1_8_2","doi-asserted-by":"publisher","DOI":"10.3233\/JAD-142853"},{"key":"e_1_3_1_9_2","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0009505"},{"key":"e_1_3_1_10_2","doi-asserted-by":"publisher","DOI":"10.1007\/s007020170024"},{"key":"e_1_3_1_11_2","doi-asserted-by":"publisher","DOI":"10.1128\/MCB.22.6.1926-1935.2002"},{"key":"e_1_3_1_12_2","doi-asserted-by":"publisher","DOI":"10.1007\/s00011-005-0062-9"},{"key":"e_1_3_1_13_2","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMra0909142"},{"key":"e_1_3_1_14_2","doi-asserted-by":"publisher","DOI":"10.1002\/j.2040-4603.2016.tb00682.x"},{"key":"e_1_3_1_15_2","doi-asserted-by":"publisher","DOI":"10.1097\/MAJ.0b013e31824ba6e0"},{"key":"e_1_3_1_16_2","first-page":"3","article-title":"Vulnerable plaque formation from obstruction of vasa vasorum by homocysteinylated and oxidized lipoprotein aggregates complexed with microbial remnants and LDL autoantibodies","volume":"39","author":"Ravnskov U","year":"2009","unstructured":"RavnskovU, McCullyKS (2009) Vulnerable plaque formation from obstruction of vasa vasorum by homocysteinylated and oxidized lipoprotein aggregates complexed with microbial remnants and LDL autoantibodies. 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