Purpose

The purpose of this experiment is to see if

anti-inflammatory medication, specifically celecoxib,
can reduce Alzheimer's symptoms in Drosophila
melanogaster by targeting the buildup of amyloid
plaques in the brain.
-Alzheimers disease is one of the most prevalent diseases in
our nation, and it is important to continue to target the
specific causes of this disease and how we can use existing
treatments to help reduce harmful symptoms.

Hypothesis
If Drosophila melanogaster that have a mutant in the
Amyloid Beta A4 Precursor Protein (APP) gene and
exhibit Alzheimer's symptoms are given celecoxib, an
anti-inflammatory medication, then their Alzheimer's
symptoms will be less significant and their memories
will function better in a T-maze.

Rationale
APP is one of the three main genes that cause FAD Alzheimer's. These
mutants cause the buildup of amyloid plaques in the brain due to the
A-42 peptides. Mefenamic acid has been known to prevent the
buildup by attenuating the neurotoxicities, and celecoxib has similar
chemical properties to mefenamic acid. If this buildup is prevented,
the Alzheimers symptoms will be less significant and the fruit flies
will be able to function better.

Background Information
Alzheimer's Disease
Alzheimers disease (AD) is the most prevalent form of dementia in the
human brain. In 2010, an estimated 36 million people were living with
AD. There are two main types of AD, which can classed as familial
(FAD), (onsets at <65 years of age) and sporadic (SAD), (onsets at >65
years) FAD is often attributed to mutations in three genes, PRESENILIN
1 (PSEN1), PRESENILIN 2(PSEN2), and the AMYLOID BETA A4
PRECURSOR PROTEIN (APP). The PSEN proteins as well as the APP
proteins comprise -secretase complexes, which are responsible for the
cleavage of a number of single-pass transmembrane proteins such as
APP and NOTCH. APP is initially cleaved by - or -secretases to release
APP or APP fragments, respectively. This triggers amyloid- (A)
peptides of various lengths. The longer A-42 peptide is prone to
aggregation and is suggested to form toxic oligomers and fibrils that
eventually deposit as amyloid plaques in the brain. These amyloid
plaques trigger subsequent cellular abnormalities such as inflammation
and oxidative stress, which leads to FAD Alzheimer's.

Previous Experimentation/Celecoxib
In an experiment done in Manchester, England, and published in
August of 2016, genetically modified mice that exhibited AD symptoms
were given mefenamic acid, which is commonly used for menstrual
pain, and were put through a series of tests. The results of their tests
concluded that almost all of their symptoms were gone. It was also
concluded that mefenamic acid attenuates the neurotoxicities induced
by the A-42 peptide in a specific inflammatory pathway called NLRP3
inflammasome.

Celecoxib is an anti-inflammatory drug that is used to reduce various

forms of pain, and has been specifically used to reduce hormones.
Mefenamic acid and celecoxib are both NLRP3-selective inhibitors.

Drosophila melanogaster
Drosophila melanogaster, or fruit flies, have become commonly used as a
model organism for genetics, microbial pathogenesis, physiology, life
history evolution, and more. In fruit flies, memory consolidation
happens entirely in a brain region called the mushroom body, which is
analogous to the human hippocampus. Because of the wide knowledge
of the fruit fly genome, it has become possible to breed fruit flies that
have mutations in specific genes, including PSEN1, PSEN2, and APP.

Studies on these mutations have shown these fruit flies to have AD

symptoms, which result in differing clumping patterns and responses to
T and Y mazes

Variables
Independent: Amount of celecoxib given to D.
Melanogaster
Dependent: Performance in T-Maze
Control: D. Melanogaster without genetic mutation and D.
Melanogaster with genetic mutation without celecoxib
Constants: Size of habitats of fruit flies, amount of food,
testing materials, amount of time anesthetized,
temperature of habitat, etc.