This may require some explanation for non-experts:<\/strong><\/p>\nFatty acids are simple chains of hydrocarbon molecules, with a small \u201chead group\u201d.\u00a0 They vary in length from short chain (e.g., having eight carbons; C-8) to long chain (e.g., having 18 carbons; C-18) and usually have an even number of carbons in the chain.\u00a0 Sometimes specific carbons are connected by double bounds, instead of single bonds; these \u201cdegrees of unsaturation\u201d form kinks in the chain and change the molecule\u2019s personality.<\/p>\n
Double bond kinks can determine how fats \u201cstack\u201d or fit together.\u00a0 Fatty acids that stack well tend to be solid at room temperature and are called \u201cfats\u201d, whereas those with double bond kinks tend to require more personal space, are liquids at room temperature, and are commonly called \u201coils\u201d.<\/p>\n
Examples include: saturated fats (no double bonds), unsaturated fats (one double bond), poly-unsaturated fats (multiple double bonds), and trans- and partially hydrogenated- fats (mostly commercial food products; not healthy!), as well as \u00a0omega-3 fatty acids (often anti-inflammatory) and omega-6 fatty acids (often pro-inflammatory).<\/p>\n
For convenient storage fatty acids can be \u201chung\u201d from a glycerol molecule \u2013 like belts on a clothes hanger. \u00a0These are the monoglycerides (one hanging chain), diglycerides (two hanging chains), triglycerides (three hanging chains, good for storage and transport), or phospholipids (two hanging chains and a phosphate head group).<\/p>\n
\u201cLipid\u201d is a very general term. \u00a0Lipids are, technically, anything similar that doesn\u2019t dissolve easily in water \u2013 such as fatty acids, waxes, sterols, fat-soluble vitamins (A, D, E, and K), monoglycerides, diglycerides, triglycerides, and phospholipids.<\/p>\n
By the way cholesterol is not a fat.\u00a0 It has a basic steroid structure, and is synthesized differently.<\/p>\n
Brain tissues usually prefer to burn sugars as fuel.\u00a0 Burning fats as fuel first requires that larger triglycerides and longer chain fatty acids be trimmed to a size that can enter the mitochondria.\u00a0 Then is requires beta-oxidation of shorter-chain fatty acids inside mitochondrial matrix, a process that is slower and can produce more toxic reactive oxygen species (ROS) than the burning of sugars.<\/p>\n
You\u2019ll recall that fatty acids can be obtained from the diet and transported in the blood as triglycerides. \u00a0Triglycerides are \u201coily\u201d and not soluble in blood plasma; hence they are circulated (along with cholesterol) inside tiny lipoprotein particles.\u00a0 These particles include the familiar LDL (the \u201cbad\u201d cholesterol carrier) and HDL (the \u201cgood\u201d cholesterol carrier), and many others. \u00a0The liver is one of the main sources of cholesterol and lipids and acts as a distribution hub to build, export, and recycle apolipoprotein particles.<\/p>\n
These particles contain some proteins \u2013 these serve as a scaffolding to help shape the particles into hollow spheres and also acts as an address label of sorts.\u00a0 Cells hoping to import cargo carried in lipoprotein particles display receptors to these proteins on their surfaces \u2013 and snag the particles as they pass by.\u00a0 ApoE (apolipoprotein E) is one of these proteins, present on the surface of many (but not all) types of lipoprotein particles.\u00a0 The apoe4 version of this protein differs only by one or two amino acids, but this give the molecule a different shape and different binding tendencies.<\/p>\n
These familiar types of lipoprotein particles produced primarily by the liver – LDL, VLDL, IDL, and HDL – do not usually penetrate the blood-brain barrier.\u00a0 Thus, the brain is \u201ccut-off\u201d from dietary fats and lipids.\u00a0 Instead the brain produces its own fats, lipids, and cholesterol and shares them among the various types of brain cells in analogous lipoprotein particles that occur only in the brain. \u00a0However, the apoe4 protein is a key component of lipoprotein particles found both inside and outside of the brain.<\/p>\n
In some cases, brain cells that are particularly hungry for fats to burn as fuel can end up breaking down the protective myelin sheaths of neurons into free fatty acids.\u00a0 This would be problematic, of course.<\/p>\n
Dr. Johnson noted the Dr. Alois Alzheimer observed “lipid droplets” in the brain of patients in 1907. Dr. Johnson\u2019s research group wondered if these \u201cdroplets\u201d were accumulations of fats and they wondered if individuals carrying apoe4 genes, and having a higher risk of developing LOAD, accumulated more lipid droplets in brain tissues. By analyzing brain tissues, they found interesting differences: apoe4 brain cells accumulation more droplets, but they are also smaller in diameter compared to apoe3 brain cells.<\/p>\n
This might be explained in part by observation that apoe4 cells have lower activity of ATP-binding cassette transporters (ABC transporters) which facilitate lipid efflux from cells. \u00a0ABC transporters load fats and lipids into lipoprotein particles for export; the presence of apoe4 reduces this, leaving apolipoproteins underinflated (or \u201cpoorly lipidated\u201d, to use the technical term).\u00a0 This could explain the group\u2019s observation.\u00a0 It would be expected that lipid droplets would accumulate inside apoe4 cells if lipids and fatty acids could not be exported as rapidly.<\/p>\n
Dr. Johnson\u2019s group noted that the accumulation of small lipid droplets in apoe4s worsen with age.<\/p>\n
In another set of experiments, they fed apoe4 brain cells fatty acids labeled with radioactive carbon (14<\/sup>C) – a useful way to trace the path of these compounds in cells.\u00a0 They found that apoe4 cells were indeed burning more fatty acids by beta-oxidation in mitochondria, supporting their hypothesis.<\/p>\nTo explore this further they conducted metabolic experiments on 94 human subjects (all <55 years old and healthy; 33 of these carried at least one copy of the apoe4 gene). \u00a0The researchers recorded the subject\u2019s metabolic activity \u2013 including their respiratory exchange ratio – at rest, then after consuming sugary drinks. \u00a0They found that subjects without apoe4 genes (including those with the apoe2 genes, which is protective against LOAD) burned the sugars easily.\u00a0 They showed the typical increase in oxygen uptake that is expected when subjects are burning sugars as fuels. \u00a0On the other hand, subjects with apoe4 genes did not metabolize sugars as well; they exhibited no increase in oxygen uptake or usage.<\/p>\n
Their conclusion from this collection of experiments – some of which were recently published – was that the data support the original theory: apoe4 cells process sugars poorly and seem to use more fatty acids as fuel to compensate.<\/p>\n
Dr. Johnson compared the metabolism of apoe4 astrocyctes and microglia to the “Warburg effect” seen in cancerous tumors.\u00a0 As mentioned previously many types of cancerous cells run glycolysis without the citric acid cycle and OXPHOS.\u00a0 This process is fast but inefficient.\u00a0 It churns out lactate acid as a waste product. \u00a0He mentioned that a \u201chigh fat diet\u201d made this more pronounced.\u00a0 NOTE: a \u201chigh-fat diet\u201d usually refers to a poor-quality diet akin to a \u201cSuper-size Me\u201d-type Standard American Diet, which is appropriately abbreviated as S.A.D.<\/p>\n","protected":false},"excerpt":{"rendered":"
Alzheimer\u2019s Disease: Tipping the energy balance Alzheimer\u2019s Afternoons Seminar Series (March 26) Lance Johnson The Alzheimer\u2019s Afternoons Seminar Series started off with a seminar by Dr. Lance Johnson…<\/p>\n","protected":false},"author":1263,"featured_media":1075,"comment_status":"closed","ping_status":"closed","sticky":false,"template":"","format":"standard","meta":{"footnotes":""},"categories":[79033],"tags":[],"class_list":["post-1074","post","type-post","status-publish","format-standard","has-post-thumbnail","hentry","category-alzheimers-afternoons-summaries"],"_links":{"self":[{"href":"https:\/\/blogs.dickinson.edu\/arnoldt\/wp-json\/wp\/v2\/posts\/1074","targetHints":{"allow":["GET"]}}],"collection":[{"href":"https:\/\/blogs.dickinson.edu\/arnoldt\/wp-json\/wp\/v2\/posts"}],"about":[{"href":"https:\/\/blogs.dickinson.edu\/arnoldt\/wp-json\/wp\/v2\/types\/post"}],"author":[{"embeddable":true,"href":"https:\/\/blogs.dickinson.edu\/arnoldt\/wp-json\/wp\/v2\/users\/1263"}],"replies":[{"embeddable":true,"href":"https:\/\/blogs.dickinson.edu\/arnoldt\/wp-json\/wp\/v2\/comments?post=1074"}],"version-history":[{"count":0,"href":"https:\/\/blogs.dickinson.edu\/arnoldt\/wp-json\/wp\/v2\/posts\/1074\/revisions"}],"wp:featuredmedia":[{"embeddable":true,"href":"https:\/\/blogs.dickinson.edu\/arnoldt\/wp-json\/wp\/v2\/media\/1075"}],"wp:attachment":[{"href":"https:\/\/blogs.dickinson.edu\/arnoldt\/wp-json\/wp\/v2\/media?parent=1074"}],"wp:term":[{"taxonomy":"category","embeddable":true,"href":"https:\/\/blogs.dickinson.edu\/arnoldt\/wp-json\/wp\/v2\/categories?post=1074"},{"taxonomy":"post_tag","embeddable":true,"href":"https:\/\/blogs.dickinson.edu\/arnoldt\/wp-json\/wp\/v2\/tags?post=1074"}],"curies":[{"name":"wp","href":"https:\/\/api.w.org\/{rel}","templated":true}]}}
![\"b2\"](\"http:\/\/blogs.dickinson.edu\/arnoldt\/files\/2020\/04\/banner2-300x169.gif\")
<\/a><\/p>\n