Cerebral glucose disturbances may influence the development of Alzheimer’s disease. Wilmarie Morales SotoAbstract: Alzheimer’s is a progressive brain disease that is affecting over 5.1 million Americans.New avenues in current research are finding that deficiencies in the glucose metabolisms maycause neurodegeneration, and evidently Alzheimer’s. Normal brain activity, such as learningand memory, depend on working neurons. In turn, neurons are highly dependent on glucose inorder to function properly. Glucose deficient neurons die, affecting cognitive brain function. Thismay be caused by faulty glucose transports to the brain and hyperphosporylation of the tauprotein. The replacement of glucose for artificial sweeteners may have a relation to memory lossand deficient glucose metabolism.Introduction disease processes of Alzheimer’s disease: amyloid plaques (abnormal clumps that Alzheimer is a progressive brain contain remnants of neurons and otherdisease that mainly affects those from the nerve cells), neurofibrillary tangles (tanglesages of sixty to eighty. Alzheimer’s disease of proteins that inhibit neural function), and(AD) causes the loss of cognitive functions- loss of connections between neurons andsuch as thinking, remembering and the brain. These elements cause toxicreasoning-and behavioral abilities. It is the changes in the brain that decay and killmost common cause of dementia amongst neurons. As more neurons begin to die,people age sixty-five and older. areas in the brain begin to shrink. This There are three major peculiarities in continues spreading throughout the brainthe brain that are associated with the
until all brain tissue has shrunk significantly For these reasons, research in thisand the body begins to shut down. area has grown significantly in the last few decades. It has developed to a point where There are three main stages to scientists are looking beyond treatingAlzheimer’s disease: mild, moderate, and symptoms, and are now trying to addresssevere. Mild AD is mainly characterized by underlying disease processes.the loss of memory and changes incognitive functions. Most AD patients arediagnosed during this stage. Moderate AD Glucose involvement in ADinvolves the damage of brain areas that developmentcontrol language, reasoning, sensoryprocessing, and conscious thought. By the In recent years, research has beentime a person reaches the severe AD stage, focusing on the areas of glucosealmost the entire brain has been affected metabolism and its relationship to Alzheimer.and the person has reached a vegetative It is well known that glucose is the mainstate. source of fuel for the brain. In order for the brain to function properly it must have a It is estimated that around 5.1 million certain amount of glucose available.Americans may have Alzheimer, and by Neurons are unable to produce a sufficientmidcentury this figure will reach 16 million amount of glucose and they have a limited(ADEAR, 2011). The cause of AD is supply they can store. Consequently, theunknown, and,therefore, no cure has been brain finds itself highly dependent on thedeveloped. There are several drugs that peripheral system for a constant supply oftreat a number of Alzheimer symptoms, but glucose (Haley et al, 2006). The brain’sunfortunately these drugs do nothing to cognitive functions, that is, the brain’s abilitydelay the prognosis of the disease.
to learn and remember, is highly dependent Inefficient glucose transport to theof a constant, uninterrupted flow of glucose. brain causes an In order to affirm glucose’s abnormalhyperphosphorylation ofinvolvement in Alzheimer’s disease, Haley tau in AD brains.A.P. et al. (2006)examined glucose As mentioned previously, brainmetabolism in the region of the neurons are unable to synthesize their ownhippocampus. They took several volunteers, glucose and they are fully dependent on theeight with AD and twenty-eight healthy blood’s transport of glucose to the brain.volunteers. All patients were given an oral Glucose transporters (GLUTS) facilitate thisglucose dosage and were then examined transport, being able to go through theusing H MRS to measure glucose blood-brain barrier (Liu et al, 2007). Thereconcentrations. They were able to are 14 different glucose transports that havedetermine that, in contrast to the healthy been identified in the body, four of whichadults, the AD patients showed an have been directly linked to the brain;increasingly high hippocampal glucose GLUT-1 (responsible for transportingconcentration post glucose ingestion, which glucose from the blood to extracellularsuggests that glucose does, in fact, directly space in the brain), GLUT-2 (has beenrelates to AD. identified in brain astrocytes), GLUT-3 In this paper we will focus on several (transports glucose from extracellular spacestudies being done on the relationship in the brain to neurons), and GLUT-4 (isbetween disturbances in cerebral glucose found inside neurons and is insulinmetabolism and if, in fact, these intolerant). An insufficiency in GLUTs 1 anddisturbances cause Alzheimer’s disease. 3 has been detected in AD and thereby bringing many to believe that this may be
the reason for deficiencies in glucose charge of glucose metabolism regulationmetabolism (Liu et al. 2007). (Liu et al. 2007). The decrease in glucose transports causes tau to become In their research, Liu Y. et al. (2007) hyperphosphorylated causing deficienciescompared GLUTs 1-4 and evaluated their and abnormalities in glucose metabolism.alterations in AD brains. They also took on Glucose metabolism then becomesthe task of evaluating if the abnormalities in impaired, which in turn triggersGLUTs 1 and 3 had any effect in glucose neurodegeneration.metabolism in the brain. By applying several antibodies andby administering western blots and immune- Can artificial sweeteners impede adot-blot analysis to both healthy brain and proper glucose metabolism function?AD brain tissue they were able to conclude As it has been continuously affirmed,that the levels for all four GLUTs were cognitive function is highly dependent onaltered differently in the brain. The levels of glucose metabolism and adequate glucoseGLUTs 1 and 3 were significantly lower in levels in the brain. Knowing this, theAD brains than in normal healthy brains. question of whether artificial sweeteners,Another significant and surprising finding such as aspartame, may causewas that GLUT-2 was highly increased in inefficiencies in the necessary amount ofAD brains. glucose to the brain has continuously been They were also able to determine brought up. Although not one hundredthat the decrease in GLUTs 1 and 3 held a percent confirmed, new developments aresignificant tie to tau phosphorylation. This inclining researcher, towards agreeing thatfinding was remarkably important. Tau yes, artificial sweeteners may have somephosphorylation is important because it is in
involvement in glucose deficiencies in the immediately before the word list wasbrain (Messier, 2004). presented (immediate anterograde), the other that would involve a time laps Sünram-Lea et al. (2002) underwent between the ingestion of the drink and thea research project where they intended to presentation of the word list (delayeddetermine whether glucose had an effect on anterograde), and finally the last conditionmemory performance. For their study they would involve the participants to administergathered a group of sixty adults, thirty of the drink immediately after the presentationwhich would be administered glucose of the word list (immediate retrograde). Thesweetened drinks (25g of pure glucose) and results showed that there were somethirty who would be administered aspartame significant improvements in the overallsweetened drinks. Each group was required scoring of those who were administered theto memorize a list of words and later identify glucose versus the aspartame drink. Theseall the words they remembered. The testing findings provide evidence that glucose is infocused on three main conditions: one being fact related to memory.that the drink would be administered The findings of the relationships between glucose, neurodegenaration andDiscussion memory are extremely significant, especially Research in regards to Alzheimer’s to those individuals with diabetes and otherdisease and glucose metabolism is currently diseases that require a significant decreasenew and still has a long way to go. These in the consumption of glucose. It’s highlynew developments in glucose metabolism recommended that future research focusesand AD are very significant for science, and on studies regarding Alzheimer incidence inAD research should continue to focus on diabetic patients versus patients who have athis particular area. normal non-glucose reducing diet. These
studies could lead to new and better 2. Haley A.P., Knight-Scott J., Simnadapproaches for treatments, not just for AD V.I., Manning C.A., 2006. Increasedbut for other glucose related diseases. glucose concentration in the hippocampus in early Alzheimer’s All studies done so far involve low disease following oral glucoseglucose levels in the brain. Future studies ingestion. Magnetic Resonanceshould focus on the processes of glucose Imaging, 715-720.metabolism in the brain and try to determine 3. Liu Y., Liu F., Iqbal K., Grundke-if AD is related to a low consumption of Iqbal I., Gong C., 2007. Decreasedglucose or just the brains inability to glucose transporters correlate tometabolize glucose properly. abnormal hyperphosphorylation of It is imperative that AD research tau in Alzheimer’s disease. FEBScontinues to be developed and perfected in Leters, 359-364.order to prevent the number of potential AD 4. Sünram-Lea S., Foster J.K, Durlachdevelopers from rising. With the P., Perez C., 2002. The effect ofdevelopments done so far researchersfind retrograde and terograde glucosethemselves closer to the answer of what administration on memoryactually causes Alzheimer-and maybe one performance in healthy young adults.step closer to finding a cure. Behavioral Brain Reaserch, 505-516. 5. Messier C., 2004. GlucoseReferences: improvement of memory: a review. 1. ADEAR, 2011.Alzheimer’s Disease: European Journal of Pharmacology. Unraveling the Mystery. [Internet] Vol. 490. 33-57. [http://www.nia.nih.gov/Alzheimers/P ublications/Unraveling/]