Anthony

Pulido
ENGW3307
Unit 1 Draft 1
2/27/15
Word count: 800
TBD
The Connection between Alzheimers and Diabetes
Abstract
[to come]

Introduction

Alzheimers disease (AD) and Type 2 diabetes mellitus (T2DM) are two

widely known diseases with no cure. Alzheimers is a neurodegenerative disease

characterized by dementia, while T2DM is a metabolic disorder reflected
characterized by an issue with the uptake of glucose. Despite these differences, in
recent years there have been comparisons describing Alzheimers as Type 3
diabetes mellitus.

Multiple forms of treatment for diabetes have been shown to treat some of

the effects of Alzheimers. Intranasal insulin has been shown to have an attenuating
affect at multiple steps in the pathology of insulin [intranasal]. The introduction of
intranasal insulin works to impede insulin resistance in the central nervous system.
The intranasal insulin also prevents the decrease of brain insulin expression, insulin
levels in the cerebrospinal fluid, and brain insulin receptor expression. In turn,
intranasal insulin decreases neurotoxicity and synapse loss, which lead to cognitive
impairment and neurodegeneration, the major characteristics of Alzheimers
disease [Intranasal]. When testing the antidiabetic drugs, Metformin, Metformin
with Sulphonylureas, Metformin with Rosiglitazone, and Rosiglitazone on separate
patients, some patients showed decreased risk of dementia, less impairment of
brain metabolism, and improvement of working memory [antidiabetic drugs].
Meanwhile, intranasal insulin gave the most evident improved cognition in the
patients tested [antidiabetic drugs].

[should I give more diabetes and insulin pathway mechanism explanation?]

The symptoms of T2DM have been believed to cause AD. Low brain insulin

levels impact the brain glucose metabolism of the brain, which is further impacted
by the brains decreased responsiveness to insulin [antidiabetic drugs]. The
increased insulin resistance caused by diabetes is further impacted by an increase in
the number of advanced glycation end products.

Genetic Findings

Microarray data was made with AD and non-AD. The array is made using a

clustered heat map. The map takes clusters of related RNA transcripts, in this case
from the hippocampus, the temporal cortex, and the frontal cortex. The map
contains complimentary strands of RNA to certain expressible genes, and when
exposed and bound to the expressed RNA, gives off a signal. The heat map can show
if there is a high concentration of RNA at each cluster, which would indicate
expression of a gene cluster. This can be used to cross reference the expression of
multiple genes together, to determine certain conditions, or correlations between
clusters, to indicate certain diseases, such as AD [Cereb cortex].
The same 1387 hippocampal transcript clusters were mapped in the frontal
cortex and the temporal cortex, as well as the hippocampus. The heat map showed
distinctions between the AD and non-AD patients. The hippocampus, the temporal
cortex, and the frontal cortex all showed distinct clustering in the AD cases that
were not seen in the non-AD cases. The heat map results indicate a similar set of
genes being expressed in the hippocampus, temporal cortex, and frontal cortex at
different concentrations in AD cases than they are in non-AD cases. The genes
expressed differently in AD cases included greater expression of some genes, but
also decrease of others. Results showed a number of the gene clusters affected
expressed proteins in the insulin pathway [Cereb cortex].
When testing mice with AD, there was a significant decrease in the
concentration in Pcsk1, which is important in the insulin pathway because it helps in
the pathway for cleaving proinsulin, producing insulin. Multiple PCSK proteins in
the hippocampus of AD cases were altered in the human genes as well. The human

cases were tested for the prevalence of PCSK proteins using microarray and a
quantitative form real time PCR to increase the amount of genetic material. The
study showed both the proteins and mRNA for PCSK1 and PCSK2 were depleted in
cases with AD [cereb cortex].
Patients were given insulin and tested for the prevalence of the upregulated
proteins in AD cases. Four different proteins that are typically upregulated in AD
cases, did not increase in expression, and some binding activity was attenuated as
well. Essentially, an insulin treatment counteracted AD symptoms. Genes in the
insulin pathway that were downregulated in AD cases, were silenced in non-AD
cases to show the affected insulin pathway, further showing more connection with
AD in brains with insulin issues [Cerebral cortex].
[this needs other recent papers with genetic support for a case of diabetes
and AD connection]

Protein Correlation

Many studies have been done to directly correlate the proteins in the insulin

pathway affected by diabetes to affects on the physiology of the brain. Insulin itself
and insulin-like growth factor (IGF) receptors are crucial in cell metabolism. These
IGF receptors on the cell surface respond to insulin to initiate the insulin pathway
[Insulin and insulin-like proteins].

(insulin and insulin-like)

(GLP)

Acknowledgements
[to come]

Bibliography
Cereb cortex
Intranasal

Antidiabetic
Insulin and insulin-like