Cerebral glucose disturbances may influence the development of Alzheimer’s disease.

Wilmarie Morales SotoRISE ProgramDecember 1, 2011

What is Alzheimer?

Alzheimer is a progressive brain disease.

It is a type of dementia that causes problems with memory, thinking, behavior, and other cognitive functions.

It mainly affects those from the ages of sixty to eighty.

(ADEAR )

Characteristics of an AD Brain AD brains are

significantly smaller than normal brains and they contain disrupted brain tissue.

Three main abnormalities:

1. amyloid plaques2. neurofibrillary tangles 3. loss of connections

between neurons and the brain.

Three main abnormalities in AD brains:

Amyloid plaques- abnormal clumps that contain remnants of neurons and other nerve cells.

Loss of connection between neurons and the brain.

Neurofibrillary tangles (transport system, held together by tau, collapses and desintigrates)

Alzheimer's Disease Stages: Stage 1:

Mild AD▪ is mainly characterized by the

loss of memory and changes in cognitive functions.

Stage 2: Moderate AD▪ damage of brain areas that

control language, reasoning, sensory processing, and conscious thought.

Stage 3: Severe AD▪ almost the entire brain has been

affected and the person has reached a vegetative state.

It is estimated that around 5.1 million Americans may have Alzheimer, and by midcentury this figure will reach 16 million.

The cause of AD is unknown, and, therefore, no cure has been developed.

(ADEAR )

Glucose involvement in AD development

Glucose is the main source of fuel for the brain.

Neurons are unable to produce a sufficient amount of glucose and they have a limited supply they can store.

The brain’s cognitive functions are highly dependent of a constant, uninterrupted flow of glucose.

Glucose metabolism in the region of the hippocampus was examined.

All patients were given an oral glucose dosage and were then examined using H MRS to measure glucose concentrations.

(Haley et al 2006)

Research

Results:

The results indicate that the levels of glucose are highly related with Alzheimer’s Disease

AD Patients Healthy Elderly

Healthy Young

N 8 14 14

Pre-Glucose

89.96 ± 7.47

82.14 ± 7.25

76.23 ± 4.49

Post-Glucose

139.43±57.81

158.29±30.50

115.08±27.12

Inefficient glucose transport to the brain causes an abnormal hyperphosphorylation of tau in AD brains. Glucose transporters (GLUTS) are vessels

that facilitate glucose transport to the brain, since they can go through the blood brain barrier.

Currently there are 14 known GLUTS in the human body.

Four of them have been found in the brain.

(Liu et al,. 2007)

GLUT1 Responsible for transporting glucose from

the blood to extracellular space in the brain.

GLUT2 Has been identified in brain astrocytes.

GLUT3 transports glucose from extracellular

space in the brain to neurons GLUT4

Is found inside neurons and it’s is insulin intolerant

AD brains have been found to be GLUT1 and GLUT3 deficient.

GLUTs 1-4 were evaluated for alterations in AD brains.

Abnormalities in GLUTs 1 and 3 were evaluated to see if they had any effect in glucose metabolism in the brain.

(Liu,. 2007)

They concluded that the levels for all four GLUTs were altered differently in the brain.

GLUT 1

GLUT 2

GLUT 3

GLUT 4

0

50

100

150

200

250

300

Healthy brainsAD brains

They found that GLUTs 1 and 3 held a significant tie to tau phosphorylation.

Tau phosphorylation is important because it is in charge of glucose metabolism regulation.

The decrease in GLUTs 1 and 3 causes tau to become hyperphosphorylated, this causes causing deficiencies and abnormalities in glucose metabolism.

Glucose metabolism then becomes impaired, which in turn triggers neurodegeneration.

Can artificial sweeteners impede a proper glucose metabolism function?

Knowing that cognitive function is highly dependent on glucose metabolism and adequate glucose levels in the brain, the question of whether artificial sweeteners, such as aspartame, may cause inefficiencies in the necessary amount of glucose to the brain has continuously been brought up.

Research

Determine whether glucose had an effect on memory performance.

They had people perform memory tests while being administered glucose before, after, and during each test.

(Sünram-Lea et al)

The results showed that there were some significant improvements in the overall scoring of those who were administered the glucose versus the aspartame drink.

These findings provide evidence that glucose has a close relation to memory.

Discussion

These new developments in glucose metabolism and AD are very significant for science, and AD research should continue to focus on this particular area.

In regards to AD and artificial sweeteners, research should continue in order to solidly prove if artificial sweeteners do really have an effect on AD.

References:

1. ADEAR.Alzheimer’s Disease: Unraveling the Mystery. [Internet] [http://www.nia.nih.gov/Alzheimers/Publications/Unraveling/]

2. Haley A.P., Knight-Scott J., Simnad V.I., Manning C.A., 2006. Increased glucose concentration in the hippocampus in early Alzheimer’s disease following oral glucose ingestion. Magnetic Resonance Imaging, 715-720.

3. Liu Y., Liu F., Iqbal K., Grundke-Iqbal I., Gong C., 2007. Decreased glucose transporters correlate to abnormal hyperphosphorylation of tau in Alzheimer’s disease. FEBS Leters, 359-364.

4. Sünram-Lea S., Foster J.K, Durlach P., Perez C., 2002. The effect of retrograde and terograde glucose administration on memory performance in healthy young adults. Behavioral Brain Reaserch, 505-516.