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1. Cerebral glucose disturbances may influence the development of
Alzheimer’s disease.
Wilmarie Morales Soto
Abstract:
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 may
cause neurodegeneration, and evidently Alzheimer’s. Normal brain activity, such as learning
and memory, depend on working neurons. In turn, neurons are highly dependent on glucose in
order to function properly. Glucose deficient neurons die, affecting cognitive brain function. This
may be caused by faulty glucose transports to the brain and hyperphosporylation of the tau
protein. The replacement of glucose for artificial sweeteners may have a relation to memory loss
and 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 other
disease that mainly affects those from the
nerve cells), neurofibrillary tangles (tangles
ages 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 and
such as thinking, remembering and
the brain. These elements cause toxic
reasoning-and behavioral abilities. It is the
changes in the brain that decay and kill
most 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 brain
the brain that are associated with the

2. until all brain tissue has shrunk significantly For these reasons, research in this
and 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 treating
Alzheimer’s disease: mild, moderate, and
symptoms, and are now trying to address
severe. Mild AD is mainly characterized by
underlying disease processes.
the loss of memory and changes in
cognitive functions. Most AD patients are
diagnosed during this stage. Moderate AD
Glucose involvement in AD
involves the damage of brain areas that
development
control language, reasoning, sensory
processing, and conscious thought. By the In recent years, research has been
time a person reaches the severe AD stage, focusing on the areas of glucose
almost 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 main
state. 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 sufficient
midcentury 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, the
unknown, and,therefore, no cure has been
brain finds itself highly dependent on the
developed. There are several drugs that
peripheral system for a constant supply of
treat a number of Alzheimer symptoms, but
glucose (Haley et al, 2006). The brain’s
unfortunately these drugs do nothing to
cognitive functions, that is, the brain’s ability
delay the prognosis of the disease.

3. to learn and remember, is highly dependent Inefficient glucose transport to the
of a constant, uninterrupted flow of glucose. brain causes an
In order to affirm glucose’s abnormalhyperphosphorylation of
involvement in Alzheimer’s disease, Haley tau in AD brains.
A.P. et al. (2006)examined glucose
As mentioned previously, brain
metabolism in the region of the
neurons are unable to synthesize their own
hippocampus. They took several volunteers,
glucose and they are fully dependent on the
eight 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 this
glucose dosage and were then examined
transport, being able to go through the
using H MRS to measure glucose
blood-brain barrier (Liu et al, 2007). There
concentrations. They were able to
are 14 different glucose transports that have
determine that, in contrast to the healthy
been identified in the body, four of which
adults, the AD patients showed an
have been directly linked to the brain;
increasingly high hippocampal glucose
GLUT-1 (responsible for transporting
concentration post glucose ingestion, which
glucose from the blood to extracellular
suggests that glucose does, in fact, directly
space in the brain), GLUT-2 (has been
relates to AD.
identified in brain astrocytes), GLUT-3
In this paper we will focus on several (transports glucose from extracellular space
studies being done on the relationship in the brain to neurons), and GLUT-4 (is
between disturbances in cerebral glucose found inside neurons and is insulin
metabolism and if, in fact, these intolerant). An insufficiency in GLUTs 1 and
disturbances cause Alzheimer’s disease. 3 has been detected in AD and thereby
bringing many to believe that this may be

4. the reason for deficiencies in glucose charge of glucose metabolism regulation
metabolism (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 deficiencies
compared GLUTs 1-4 and evaluated their
and abnormalities in glucose metabolism.
alterations in AD brains. They also took on
Glucose metabolism then becomes
the task of evaluating if the abnormalities in
impaired, which in turn triggers
GLUTs 1 and 3 had any effect in glucose
neurodegeneration.
metabolism in the brain.
By applying several antibodies and
by administering western blots and immune- Can artificial sweeteners impede a
dot-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 on
altered differently in the brain. The levels of
glucose metabolism and adequate glucose
GLUTs 1 and 3 were significantly lower in
levels in the brain. Knowing this, the
AD brains than in normal healthy brains.
question of whether artificial sweeteners,
Another significant and surprising finding
such as aspartame, may cause
was that GLUT-2 was highly increased in
inefficiencies in the necessary amount of
AD brains.
glucose to the brain has continuously been
They were also able to determine
brought up. Although not one hundred
that the decrease in GLUTs 1 and 3 held a
percent confirmed, new developments are
significant tie to tau phosphorylation. This
inclining researcher, towards agreeing that
finding was remarkably important. Tau
yes, artificial sweeteners may have some
phosphorylation is important because it is in

5. involvement in glucose deficiencies in the immediately before the word list was
brain (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 the
a research project where they intended to
presentation of the word list (delayed
determine whether glucose had an effect on
anterograde), and finally the last condition
memory performance. For their study they
would involve the participants to administer
gathered a group of sixty adults, thirty of
the drink immediately after the presentation
which would be administered glucose
of the word list (immediate retrograde). The
sweetened drinks (25g of pure glucose) and
results showed that there were some
thirty who would be administered aspartame
significant improvements in the overall
sweetened drinks. Each group was required
scoring of those who were administered the
to memorize a list of words and later identify
glucose versus the aspartame drink. These
all the words they remembered. The testing
findings provide evidence that glucose is in
focused on three main conditions: one being
fact related to memory.
that the drink would be administered
The findings of the relationships
between glucose, neurodegenaration and
Discussion
memory are extremely significant, especially
Research in regards to Alzheimer’s to those individuals with diabetes and other
disease and glucose metabolism is currently diseases that require a significant decrease
new and still has a long way to go. These in the consumption of glucose. It’s highly
new developments in glucose metabolism recommended that future research focuses
and AD are very significant for science, and on studies regarding Alzheimer incidence in
AD research should continue to focus on diabetic patients versus patients who have a
this particular area. normal non-glucose reducing diet. These

6. studies could lead to new and better 2. Haley A.P., Knight-Scott J., Simnad
approaches for treatments, not just for AD V.I., Manning C.A., 2006. Increased
but for other glucose related diseases. glucose concentration in the
hippocampus in early Alzheimer’s
All studies done so far involve low
disease following oral glucose
glucose levels in the brain. Future studies
ingestion. Magnetic Resonance
should 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. Decreased
glucose or just the brains inability to
glucose transporters correlate to
metabolize glucose properly.
abnormal hyperphosphorylation of
It is imperative that AD research tau in Alzheimer’s disease. FEBS
continues to be developed and perfected in Leters, 359-364.
order to prevent the number of potential AD 4. Sünram-Lea S., Foster J.K, Durlach
developers from rising. With the P., Perez C., 2002. The effect of
developments done so far researchersfind retrograde and terograde glucose
themselves closer to the answer of what administration on memory
actually 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. Glucose
References:
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/]