International Journal of Engineering and Creative Science, Vol. 1, No.

1, 2018
www.ijecs.net

Alzheimer: A disease of brain

Ujjwala Supe1, Jayant Supe2
1
Plant Tissue Culture Laboratory, Department of Biotechnology, St. Thomas College, Bhilai, Dist-Durg- 490006,
2
Department of Civil Engineering Rungta college of Engineering and Technology, Bhilai

Abstract – Reviewed here are certain main causes, effects and preventions of this deadly disease within our scope of
general observation. To start with the interesting story of describing this disease first in 1906 and subsequently, discussed
are main causes, risk factors involved and different early warning signs of Alzheimer. A few simple symptoms, causes and
some effective treatment is concluded in this article.

Keywords- Alzheimer disease, Amyloid plaques, Apoliopoprotein E 14 gene,Huperzine

II- HISTORY
I- INTRODUCTION
Alzheimer, is the most widespread Alzheimer‟s disease Year Discoveries related Alzheimer
of a large category of disorders known clinically as
dementias. The main features of dementia are a 1898 Austrian neurologist Emil Redlich relates
progressive deterioration of thinking and memory. senile plaques with senile dementia.
Common symptoms include a gradual loss of memory, 1906 At the 37th annual conference
problems with reasoning or judgment, disorientation, of German psychiatrists, physician Alois
difficulty in learning, loss of language skill etc 2. People Alzheimer describes the case of
with dementia also experience changes in their patient Auguste Deter, who has Alzheimer‟s
personalities and behavioral problems. It has recently disease profound memory loss, unfounded
been shown that Alzheimer is the leading cause of suspicions about her family, and other
dementia – in fact 70% of dementias are due to worsening psychological changes. In her brain
Alzheimer. Apart from deterioration of thinking, in at autopsy, Alzheimer sees dramatic shrinkage
Alzheimer there can also be behavioral changes such as and abnormal deposits in and around nerve
agitation, aggression and an inability to find the way cells4.
even in familiar surroundings1. The cumulative effect of 1910 German psychiatrist Emil Kraepelin, a
these changes becomes distressing both to the individual colleague of Alzheimer, first names
and their families. According to statistics, as many as 2-4 "Alzheimer's Disease" in the eighth edition of
% of global population of 65 years of age and older have his book Psychiatrie.
Alzheimer.As many as 20%of population over85 years 1931 German electrical engineer Max Knoll and
age have the disease.It should be stressed that German physicist Ernst Ruska co-invent
Alzheimer‟s disease knows no social, economic, ethnic the electron microscope, which can magnify up
or geographical boundaries; eventually those affected are to 1 million times.
unable to care for themselves and need help with all 1968 Researchers develop the first validated
respects of daily life. The magnitude of this disease is so measurement scale for assessing cognitive and
huge that it is estimated to be 18 million people affected functional decline in older Alzheimer‟s disease
worldwide with Alzheimer3. ults.
1976 Alzheimer's disease is recognized as the most

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common form of dementia. 2001 Galantamine is approved for use in mild to

moderate stages of Alzheimer's disease8
1976 Three teams, led by Elaine Perry, D.M. Bowen,
2003 Memantine is approved for use in moderate to
– and P. Davies demonstrate the alteration of
severe stages of Alzheimer's disease.
1977 central cholinergic systems in Alzheimer's
5 2003 The National Alzheimer's Disease Genetics
disease .
Study begins. Blood samples are collected from
1984 Researchers George Glenner and Caine
families with several members who developed
Wong identify protein known as amyloid beta,
Alzheimer's late in life to identify Alzheimer‟s
the main component of the amyloid
disease ditional Alzheimer's risk genes.
plaques found in the brains of Alzheimer
2006 Rivastigmine is approved for use in all stages
patients.
of Alzheimer's disease.
1986 Belgian physician Jean-Pierre
2010 A database is launched containing information
Brion identifies Tau protein as a key
of more than 4000 patients with Alzheimer's
component of neurofibrillary tangles, the
disease who participated in 11 pharmaceutical
second pathological hallmark of Alzheimer's
industry-sponsored clinical trials of
disease and another prime suspect in nerve cell 9
Alzheimer's treatments
degeneration.
2012 Multinational research consortium Dominantly
1987 Amyloid precursor protein (APP) is discovered.
Inherited Alzheimer Network (DIAN),
It is the first gene with mutations found to
launches the first major clinical trial
cause an inherited form of Alzheimer's
testing pharmacotherapy to prevent the onset
disease6.
of Alzheimer‟s disease symptoms in people
1992 Presenilin-1 (PS-1) is identified. It is the
who inherited an autosomal dominant mutation
second gene with mutations found to cause
putting them at high risk for the disease.
inherited Alzheimer's disease. Variations in this
2013 International Genomics of Alzheimer‟s Project
gene are the most common cause of inherited
(IGAP) researchers identify 20 genetic
Alzheimer's.
variations associated with increased risk
1993 Presenilin-2 (PS-2) is discovered. It is the third
of Alzheimer‟s disease.
gene with mutations found to cause
2014 Researchers at Rush University come to the
inherited Alzheimer's disease.
conclusion that rates of death caused by
1993 Apolipoprotein E-e4 (APOE4) is discovered. It
Alzheimer‟s disease are found to be much
is the first gene variation found to increase risk
higher than reported on death certificates. The
of Alzheimer's disease and remains the risk
study is performed on organs donated from
gene with the greatest known
2,566 persons aged 65 years and older without
1993 The United States Food and Drug Alzheimer‟s dementia at baseline10.
disease ministration (FDA) 2016 According to Alzheimer Disease International,
approves tacrine (Cognex) as the first drug nearly 44 million people have Alzheimer‟s
specifically targeting Alzheimer's disease or a related dementia at a worldwide
disease memory and thinking symptoms. level1
1995 Researchers announce the first transgenic
mouse model that developed Alzheimer-like
III- CAUSES
brain pathology, by inserting one of the
human APP genes linked to a rare, inherited Alzheimer‟s disease is mainly characterized by
form of Alzheimer's disease progressive death of brain cells. This result from two
1996 Donepezil is approved for use in all stages abnormal structures in the brain: Amyloid plaques,
of Alzheimer's disease. which are clumps of protein fragments that accumulates
1999 First report announcing that injection of outside of cells and Neurofibrillary tangles which are
transgenic "Alzheimer" mice with beta-amyloid clumps of altered protein inside cells12. The outline of
prevents the animals from developing plaques brains of a person with Alzheimer disease showed: 1)
and other Alzheimer's disease-like brain Here and there manyof the nerve cells start to shrink
changes. eventually disappearing 2) Amyloid plaques develop all
over the brain 3) Neurofibrillary tangles of a fine thread
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like protein called “tau” develop inside brain cells and 4)
Inflammation of the brain develops.
Research about these structures has provided clues about
why nerve cells die, but till date scientists have not been
able to determine exactly why these changes develop. In
short, no one knows exactly what causes Alzheimer‟s
disease. Most researchers agreed that the cause may be a
complex set of factors.
A few such risk factor involved are discussed below
The first identified risk factor is increasing age, Though
Alzheimer disease affects individuals in 40s and 50s,
Studies have shown that the greatest known risk for
developing Alzheimer isincreasing age. However this
does not mean that everyone living to a certain age or
beyond will get the disease.
The next identified risk factor is a genetic predisposition.
i.e., family history. Having a parent or sibling with the
disease increases an individual‟s chances of developing
Alzheimer. Alzheimer‟s disease is nearly a common
factor among older people, even if many elderly
members in a family are affected by the disease, it does
not necessarily mean that the disease is being transmitted
within the family on a purely genetic basis13.
Many mysterious diseases have also provided interesting
clues through genetic studies. Scientists have identified
certain genes, which are very strongly related to
Alzheimer. To date, three such genetic defects have been
identified in patients of Alzheimers diseases. In other
words people inheriting these genes from their parents
may getthe disease. One defect each is situated on
chromosomes 14, Chromosomes 19 and on
chromosomes 21. There may be possible genetic defects,
as yet unidentified in patients of Alzheimers disease.
These genetic defects manifest themselves by
aggregation of multiple cases of thediseases within
families affecting multiple generations. However, It
must be emphasized that the proportion of all cases of
Alzheimer which are inherited on a genetic basis is less
than 1-2% of all known cases of the diseases.
Another mechanism of genetic effect is the inheritance
of a susceptibility gene the best known susceptibility
gene is identified by medical research is the
Apoliopoprotein E 14 gene. However, inheriting this
gene does not necessarily mean that the person will get
Alzheimers disease; there are numerous patients who
have these genes and still do not yet get the disease.
Since APOE is known to affect cholesterol metabolism,
12
Research in India suggested that high fat diet, as is
typical in western countries may be one of the factors
which interact with APOE gene to increase the risk of
Alzheimer diseases in west14. Millions or dollars have
already have been spent worldwide in trying to
determine why certain people get Alzheimers diseases.
At the current stage of knowledge, it is still not possible
to predict who will get the disease. It can strike anyone
irrespective of gender, caste, creed, culture or
socioeconomic status. However, based on some
characteristics, prevention can be taken at the early stage
of the disease.
IV- SYMPTOMS
The disease is a progressive, degenerative with many
symptoms. It is important to consult a doctor or
Alzheimer‟s and related diseases society of India. If any
of these symptoms is noticed as they may be due to other
conditions such as depression, drug interaction or an
infection also15.
Symptoms commonly experienced during the early
stages of Alzheimer's disease include:
 Mild forgetfulness – especially short-term
memory loss
 Mood changes, including irritability and
anxiety
 Difficulty processing new information and
learning new things
 Loss of spontaneity and initiative
 Confusion about time and place
 Communication difficulties
 Decline in ability to perform routine tasks.
As Alzheimer‟s disease progresses the following
symptoms may develop:
 Increasing short-term memory loss and
confusion
 Difficulty recognizing family and friends
 Shorter attention span and feelings of
restlessness
 Difficulty with reading, writing and numbers
 Possibly neglectful of hygiene
 Loss of appetite
 Personality changes (eg: aggression, significant
mood swings)
 Requires increasing assistance with daily tasks.
Towards the later stages of the disease the following
symptoms may be experienced16
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 Inability to understand or use speech
 Incontinence of urine / feces
 Inability to recognize self or family
 Severe disorientation
 Increasing immobility and sleep time
V- TREATMENT OF ALZHEIMER’S DISEASE
There is no cure for Alzheimer‟s disease, and drug
therapy for the disease is still in its infancy. Approved
medications for the treatment of probable Alzheimer‟s
disease help control the symptoms of Alzheimer‟s
disease but do not slow down the progression or reverse
the course of the disease itself. At present, the mainstay
of Alzheimer‟s disease therapy is drugs that target
neurotransmitter systems in the brain. Alzheimer‟s
disease primarily damages glutamateand acetylcholine-
producing neurons and their associated synapses, and
this damage correlates well with early cognitive
symptoms of Alzheimer‟s disease17.
Acetylcholinesterase inhibitors help improve memory
function and attention in Alzheimer‟s disease patients by
interfering with the breakdown of acetylcholine, thereby
increasing the levels of the neurotransmitter at the
synapse. There are currently three FDA-approved
cholinesterase inhibitors: rivastigmine and galantamine
(for mild to moderate Alzheimer‟s disease), and
donepezil (for all stages of Alzheimer‟s
disease)18.Memantine is another FDA-approved
medication for use in moderate to severe Alzheimer‟s
disease but belongs to a different class of drugs known
as NMDA (glutamate) receptor antagonists. Both classes
of medications are generally well-tolerated, with
gastrointestinal upset, dizziness, and theAlzheimer‟s
disease ache being the most common Alzheimer‟s
disease verse effects observed. In recent years, a number
of potential disease-modifying Alzheimer‟s disease
drugs have been evaluated in clinical trials, and several
others are being evaluated in ongoing trials.
Drugs that act to decrease the amount of Ab protein in
the brain have received the most attention due to the
prominent pathogenic role ascribed to Ab in the
Alzheimer‟s disease literature. One class of such drugs
aresecretase inhibitors, which inhibit the secretase
(protease) enzymes that cleave APP to produce Ab.
Another strategy that has been attempted is by using
drugs that promote the clearance of Ab through active or
passive immunization.
Five medications are currently used to treat the cognitive
problems of Alzheimer‟s disease four
are acetylcholinesteraseinhibitors (tacrine, rivastigmine,
13
galantamine and donepezil) and the other (memantine) is
an NMDA receptor antagonist. The benefit from their
use is small. No medication has been clearly shown to
delay or halt the progression of the disease.
Huperzine A while promising requires further evidence
before its use can be recommended19.
Unfortunately, as of the writing of this article, several
completed phase three trials with different amyloid-
lowering drugs have failed to demonstrate clinical
efficacy.Various explanations have been proposed to
account for the repeated clinical trial failures observed
with these disease-modifying agents. One possibility is
that antibodies may play a less prominent or different
role in Alzheimer‟s disease pathogenesis than previously
hypothesized,an issue certain to remain controversial in
the near future. Regardless, other therapeutic strategies
for Alzheimer‟s disease are being investigated alongside
the amyloid-based therapies, although with no major
clinical successes yet to report. A promising avenue is
the development of drugs that target the abnormal tau
protein comprising the NFT. Another important source
for potential Alzheimer‟s disease drugs is the pool of
medications on the market that are already approved for
non- Alzheimer‟s disease indications, such as diabetes,
hypertension, and infectious disease. This strategy of
drug „repurposing‟ or „repositioning‟ can greatly
expedite the discovery of novel Alzheimer‟s disease
treatments and has been used in the past for other
neurodegenerative disorders (e.g., anti-viral drug
amantadine for use in Parkinson‟s disease). An
alternative explanation for the clinical trial failures is
that the trials were conducted in patients with mild to
moderate Alzheimer‟s disease 20As time passes on
mankind become more and more aware, leading towards
many fruitful discovery with detailed understanding of a
system, which might have been unknown even
sometimes back. We are still not in position to eradicate
Alzheimer totally from our society rather it is
proliferating its number of victims day to day, we can
now think about decelerating its progress by vaccines
and other possible ways.
VI-CONCLUSION
A year long campaign is focusing on research of
Alzheimer‟s disease. People are also hopeful about the
recent discovery that demands to halt the progress of
Alzheimer in brain. However, all the efforts are still
confirmed within genetically engineered and the exact
cause of the disease is still known to us.
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