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Term Paper Report On

A REVIEW ON TREATMENT OF ALZHEIMER DISEASE Submitted To

Amity Institute of Biotechnology

Amity University Uttar Pradesh Lucknow Campus

In Partial Fulfilment for the Degree of

MASTER OF SCIENCE

In

BIOTECHNOLOGY By

PRITI PAL

A7100213018

UNDER THE SUPERVISION OF

Prof Dr. Aditi Singh Amity Institute of Biotechnology

Amity University Uttar Pradesh Lucknow Campus

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Declaration

I hereby declare that term paper report entitled “A REVIEW ON

TREATMENT OF ALZHEIMER DISEASE” undertaken by me is an

authentic record of my own work carried out at Amity Institute Of

Biotechnology, Lucknow as a requirement of Internship Project for the award of

degree of M.Sc. in Biotechnology, Amity University, Lucknow, under the

guidance of Dr.Aditi Singh, Professor AIB during 01st May, 2014 to 15st July,

2014.

DATE: 15 July, 2014

PLACE: Lucknow Priti Pal

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FACULTY GUIDE APPROVAL CERTIFICATE

I, hereby declare that the term paper entitled “A REVIEW ON TREATMENT

OF ALZHEIMER DISEASE” is a record of an original work done by Ms Priti

Pal from 01-05-14 to 15-07-14 at Amity University, Lucknow. This work has

been carried out under the guidance of me, Dr. Aditi Singh, Sr. lecturer,Amity

University Lucknow.

Dr. Aditi Singh

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AMITY UNIVERSITY UTTAR PRADESH

LUCKNOW CAMPUS

PLAGIARISM FREE CERTIFICATION

This is to certify that internship project detailed below has been evaluated by

online anti-plagiarism software. The contents and material was found

satisfactory and within the permissible limit of content copied.

Name of the Student- Priti Pal

Enrollment Number- A7100213018

Program and Batch-M.Sc. Biotech III rd Sem, 2013-2015

Title of the Project-A REVIEW ON TREATMENT OF ALZHEIMER

DISEASE

Results-

Student Internal Faculty Supervisor

Date:

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Acknowledgement

The successful completion of any project would be incomplete without thanking the people

who made it possible. With all my submissiveness I thank God for his constant presence

throughout my work. It takes great pleasure in expressing a few words of gratitude and

respect to all those who helped me in completing this project work.

I am highly grateful to Dr. Rajesh Kumar Tiwari, HOI, Amity Institute of Biotechnology,

Lucknow for accepting my candidature and permitting me to undertake the dissertation work.

It is my proud privilege and pleasure to bring my deepest gratitude to my supervisor Dr.

Aditi Singh, Professor AIB, Lucknow for the constant supervision, meticulous guidance, his

ever encouragement, moral support, constructive criticism and above all most sympathetic

attitude throughout the period of investigation.

I feel great pleasure in expressing my earnest and deep sense of gratitude to Dr. .Aiti singh

Abhishek kumar, AIB for their invariable guidance, invaluable healthy instructions, constant

supervision and keen interest throug out the course.

With profound happiness, I want to pay my heartfelt regards and feelings of indebtedness

Towards the eternal love and fondness showered on me by my family.

Date: 15 July, 2014 Priti Pal

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TABLE OF CONTENTS

PARTICULARS PAGE No.

Title Page 01

Declaration 02

Faculty Guide Approval Certificate 03

Plagiarism Free Certificate 04

Acknowledgement 05

Table of Contents & List of Figures 06

Abstract & Key words 07

Introduction on Alzheimer disease

Stages of Alzheimer disease

08-10

Medication of Alzheimer disease 11-12

Research Developing in the field of treatment of Alzheimer 12-15

Future prospects of treatment of Alzheimer disease 15

Conclusion 16

References 17-18

List of figure

Fig.1. Dig showing a comparison between healthy neuron and neuron

containing plaque page 8

Fig.2. Dig showing different stages of Alzheimer disease page 10

Fig.3. Dig showing beta amyloids blood plaque page 13

Fig.4. Dig showing enzyme activity in reducing blood plaque page 14

Fig.5. Dig showing stem cell therapy in Alzheimer treatment page 15

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“A REVIEW ON TREATMENT OF ALZHEIMER DISEASE” Priti pal, Aditi Singh and Rajesh K. TiwariAMITY INSTITUTE OF BIOTECHNOLOGY AMITY UNIVERSITY UTTAR PRADESH LUCKNOW CAMPUS

ABSTRACT- Nowadays Alzheimer’s disease is the most common and hazardous

neurodegenerative disorder. Alzheimer’s disease (AD) can be featured and characterized on a

macro level as the progressive loss of brain tissue. When this disease gradually progressed or

progresses, the neurons die in a particular pattern over time. One of the early signs of

Alzheimer’s disease is memory loss, particularly short term recall. Many compounds which

are approved had different alternate diagnoses, which all are studied in relation to

Alzheimer’s disease. The aim of my study is to summarize and confer of their importance and

benefits of drugs for Alzheimer disease treatment. There are numerous drugs which are

having known toxicity profiles and can adapt for use in the different purpose, like as a

treatment for Alzheimer’s disease. There are many therapeutic drugs or treatment for the

Alzheimer disease, although there are no proven agreements and negotiations to rectify

Alzheimer disease, hypertension treatment, omega-3 fatty acid supplementation, physical

activity and cognitive engagement determine unpretentious potential. Other agents like

antioxidants vitamin E, selegiline and ginko biloba extracts have shown some benefit in

clinical trials, but their effects are is not sufficient to define clinical practice.

According to the latest study the genetically reconstruct stem cells may provide a new

improved techniques which are developed to treat Alzheimer’s disease. Genetically modified

stem cells when embed in mice bred to have sign and brain hallmarks of Alzheimer they

expand increased connections between brain cells and lessen the amyloid-beta protein that

assemble to form plagues that clog up the brain. Woman is more commonly affected by this

disease as compare to man. Many Researchers are given many researches on Alzheimer’s

disease which scrutinize many feasible technique of preventing or slowing Alzheimer’s

which involve cardiovascular treatments, antioxidants, immunization therapy, cognitive

training and physical occupation. This review covers and discusses all the basic evidence and

role of oxidative stress in Alzheimer disease development. This article discusses the public

health influence of Alzheimer including occurrence and prevalence, mortality rates, costs of

care and overall effect on caregivers and community.

KEYWORDS:- Alzheimer disease, Acetyl cholinesterase inhibitors, treatment, brain tissue.

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INTRODUCTION-

Alzheimer’s disease is a degenerative, progressive disorder which is attacks the brains nerve

cells and neurons denouement in memory loss thinking and language skills and behavioural

commutation. Those neurons that produce the brain chemical or neurotransmitter,

acetylcholine, split connections with other nerve cells and eventually depart this life. For

example:-short term memory lapse when Alzheimer’s disease first demolish nerve cells in the

hippocampus and language ability and judgment shrink when neurons expire in the cerebral

cortex. Two types of unusual contusion plug the brains of discrete with Alzheimer’s disease

beta-amyloid plagues sticky clumps of protein fragments and cellular tangles. Insoluble

twisted fibres composed substantially of the protein Tau that expansion inside the nerve cells.

Although these structure are hallmarks of the disease. Scientists are unsure whether they

genesis it or a by product of it. For people 65 and older Alzheimer’s disease is the most usual

form of dementia or loss of cognitive function. Aging is not a normal part of Alzheimer’s

disease.

Fig.1. Dig showing a comparison

between healthy neuron and neuron containing plaque

SOURCE:  http://alzheimerindia.blogspot.com/ http://www.stemcell.net.in

TERM GIVEN BY-

Dr. ALOIS Alzheimer a German physician in 1906 gave the term Alzheimer disease. In a

medical meeting he presented a case history about a 51 year old woman who suffered from an

unknown brain disorder. A brain necropsy recognized the plaques and tangles which today

are characterized as Alzheimer disease.

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CAUSES AND RISK FACTORS OF ALZHEIMERS DISEASE-

Till now there is not a single component identified as the cause of Alzheimer disease. These

are a combination of factors responsible that are age, genetic inheritance, environmental

factors, life style and overall general health. In some cases this disease develops silently

before the symptoms appear. In this one of the major factor which is been noticed is the

family background which include that the family in which a person’s brother and sister

having the alzhiemer diseases are more prone to have this disease so it can be said that

genetic or heredity matters a lot. Apart from the other things which are important are many

which include point such as mild congnitive impairment (MIC). It is also a major risk

factor which possibly is symptom is a mild condition in which a person has a measurable

problem in his or her thinking.

People who have rare genetic changes that guarantee they will develop Alzheimer disease

experience symptoms in 30s.Age is the biggest risk factor for growing Alzheimer disease. As

we grow older, we assemble more beta amyloid. The risk of Alzheimer disease doubles after

the age of 65. Further, risk factor for Alzheimer disease is genetics. Alzheimer diseases rare

form is called familial Alzheimer .It usually starts between the age of 40’S and 50’S.It passes

genetically which is autosomal dominant. Head trauma is another important risk factor for

Alzheimer disease. The loss of consciousness grows the risk of developing Alzheimer

disease. We should always wear a seat belt and helmet for our safety. In a study held in

Japan, about 1000 men and women of age 60 or above who suffered from type 2 diabetes had

an increasing risk of Alzheimer disease simultaneously to those people who don’t suffer from

the same.

Out of 10, about 8 people who suffer from Alzheimer disease also suffer from cardiovascular

diseases. Cholesterol increases the production of beta amyloid. When the levels of beta-

amyloid extends, it increases the risk of Alzheimer diseases. This is the reason that doctors

recommend statins for those people who suffer from Alzheimer disease and also to maintain

their cholesterol levels.

STAGES OF ALZHEIMER’S DISEASE-

There are mainly 7 stages of this disease, the top three main stages of Alzheimer disease are-

Mild’s Alzheimer’s

Moderate Alzheimer’s

Severe Alzheimer’

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Fig.2. Dig showing different stages of Alzhemier’s disease

SOURCE: http://www.medicinenet.com/imagecollection/alzheimers_disease_picture/picture.htm

The basic character of Mild’s Alzheimer’s disease is that the sufferer may face the problem

of short term memory loss. The duration of this disease is 2-4 years. It is difficult for the

person to recall something easily, to take some judgement or in migrating new places. It is

also not being noticed by others as it is so common.

The symptom of Moderate Alzheimer’s is that the memory loss and confusion is much more

increased. It is difficult for the sufferer to learn something new. They may change to

impulsive behaviour. The duration of this disease is 2-10 years. The person may trouble from

the misapprehension and unrestrained behaviour. Due to weakness Motility and coordination

is affected as there is austerity and shiver in it. They need succour for their daily life routine.

The symptom of Severe Alzheimer’s is that the ability of walk and sit become limited

simultaneously the ability for speech or communication also become hard for the sufferer.

The time duration is 1-3 years. They suddenly become confused about their past and present.

They become generally incapable with their verbal skills. They start depending totally upon

others. They usually suffer from Devour, Lewdness and Ailment. They usually suffer from

Phantasm & Dementia.

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MEDICATION FOR ALZHEIMER’S DISEASE-

There is no particular prevention for this disease, but the process of medication is in progress,

with the symptoms of the disease it can be cure by the available drugs. There is a worldwide

effort going on to find the ways to obtain a perfect cure for it. The treatment for the

Alzheimer’s cannot stop the problem in the mean while it can reduce the effects for the same,

it can aggravate the symptoms of dementia. In a class there are four drugs Donepezil (brand

name Aricept) Alantamine (Reminyl), Rivastigmine (Exelon), Tacrine (cognex) called

cholinesterase inhibitor consent for treatments which only treat the symptoms in the U.S.

Memantine (namenda) an NMDA receptor antagonist is a different kind of drug which can

also be helpful to use, individually or with the combination of cholinesterase inhibitor. The

clinical relevance or aspects of these effects is not clear.

Person older than 65 years usually diagnosed Alzheimer disease and its generality expand

sever decade thereafter. Approx half of the Americans of the age near to 85 years old has

Alzheimer disease.

The major two types of medication which work in different ways and is used for the

prevention of Alzheimer’s are Cholinesterase Inhibitors and Memantine, NMDA receptor

antagonist. In a class there are four drugs Donepezil (Aricept) Alantamine (Reminyl),

Rivastigmine (Exelon), Tacrine (cognex) called cholinesterase inhibitor. Memantine

(Ebixa) is the NMDA receptor antagonist.

SERVICE OF THE MEDICATION-

All the instruction for the medication is recently consent for the treatment of Alzheimer’s

disease symptoms relatively with the class of drugs use in early to moderate stage

Cholinesterase inhibitors. They instruct for the issues related with the power of retention, the

way of reasoning, Variant of judgement.

Cholinesterase inhibitors avert the malfunction of Acetylcholine. It is a chemical messenger

which is very necessary for the power of retention and the process of recognizing. While the

acetylcholine level high in nerve cell it helps to communicate among the same. The retained

aggravate symptoms for 6 to 12 months on average around 50% of person take them. Aricept

medicine is the class of Cholinesterase inhibitors which is consent to treat the stages of

Alzheimer’s disease i.e. moderate and severe.

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Memantine is authorized for the betterment of the power of retention, consciousness, dialect

and cause to accomplish an easy task. Memantine modulate the work of glutamate, which is

a different chemical messenger used in the process of memorizing and retaining.

ADVERSE EFFECT OF THIS DRUGS-

Usually, cholinesterase inhibitor and Memantine can worked without too many adverse

effects. It’s not necessary to have the same problem or do not have it for the same time

interval if they even experience it at all. The common side-effects of donepezil, rivastigmine

and galantamine are loss of appetite, nausea, vomiting and diarrhoea .Some another side

effects of the same are stomach cramps, headaches, dizziness, fatigue and insomnia. These

kind of problems like side effects are usually dislike by those who recently start following

that treatment with the lower prescribed dose at least for a last month. The side-effect of

memantine are not common and less severe than for cholinesterase inhibitor .They include

dizziness, headaches, tiredness, increased blood pressure and constipation.

Available pharmacological treatments for Alzheimer disease have limited effectiveness

are expensive and some time induce side effects.

RESEARCH DEVELOPING IN THE FEILD OF TREATMENT OF ALZHEIMER

Up-till now it was known that Alzheimer was cureless. Only few medication were been

developed in favour of treatment. But during the increasing course of time new techniques

are been developed and trials are been made in order to develop a standard treatment of this

diseases. In order to have a brief study of the treatment Alzheimer have to be studied in very

contrast. Over the past decades when all the discoveries were been going on and a better

treatment was been searching then also the drugs discoveries were found to be disappointing.

If the major feature of Alzheimer is to be noted then it is the presence of brain plaque which

is marked to be a hallmark pathological feature in Alzheimer. This brain plaque contain

primarily β-amyloid peptide, these are present in aggregates which are the main primarily

reason behind the formation of blood plaque in the brain. This β-amyloid peptide, aggregates

is one of the important reasons which cause the later stages of the disease.

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Fig.3. Dig showing beta amyloids blood plaque

Source: http://thebrain.mcgill.ca/flash/d/d_08/d_08_cl/d_08_cl_alz/d_08_cl_alz.html

In many researches which are been done in recent years have been found that the production

of insulin in body is one of the reason why Alzheimer is growing at such an alarming rate. It

was found that the decrease in the level of cerebrospinal fluid level of the insulin which

ultimately decrease the level of insulin sensitivity (insulin resistance) inside the brain. It was

also found that if the nasal insulin level is increased then it would be helpful in treating the

Alzheimer diseases.

Hence like this many other techniques are been developed since the past two decades which

include the management of the insulin inside the body and maintaining the level of it. Thus

this diseases although is incurable but still holds up a promising cure which are still been

developing.

Now some new extremity to drug is required for evolution. Translational Neuroscience pivot

on the connection between general neuroscience and the growth of advanced diagnostic and

therapeutic production that will be helpful for the sufferer to make better their lives or avert

the recurrence of brain disorder. Translational neuroscience involve comprehend preclinical

models that may become more suitable express human effeminacy and security, better

clinical tentative designs and results that will help to advance the drug growth, for more

knowledge concerning the effects of drugs on the latent disease biology the use of biomarkers

is depleted. In the beginning, translational research is achieve and after later stage

translational make approach for use the proof to collision clinical practice and to approach

the repercussion of advance therapeutics on the public health.

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Fig.4. Dig showing enzyme activity in reducing blood plaque

SOURCE: http://www.nature.com/nature/journal/v461/n7266/fig_tab/461895a_F1.html

If the research work is been talked about there has been a new criteria which was developed.

By 1984 a new guidelines were been update which was successful done by Alzheimer

Association and the National Institute of Neurological Disorder and Stroke. The updates

which were done in 1984 were mainly done by over viewing approx 40 medicinal research

institute that were working over the Alzheimer disease. Earlier also it was seen that

Alzheimer has no cure. After several researches The U.S Drug and food administration has

approved five drugs for the treating the diseases and finding out improvements. Despite of

lack disease inappropriate medication still there are several things which can be done in

respect to treatment of Alzheimer. One of the effective ways of treating these diseases is the

ACTIVE MANAGEMENT of the diseases. Proper care should be taken for such type of

patients.

According to the latest study the genetically reconstruct stem cells may provide a new

improved techniques which are developed to treat Alzheimer’s disease. Genetically modified

stem cells when embed in mice bred to have sign and brain hallmarks of Alzheimer they

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expand increased connections between brain cells and lessen the amyloid-beta protein that

assemble to form plagues that clog up the brain.

Fig.5. Dig showing stem cell therapy in Alzheimer treatment

Source: http://stemcells.nih.gov/info/basics/pages/basics6.aspx

FUTURE PROSPECTS OF TREATMENTOF ALZHIMER DISEASE

Up till now the major discoveries which are been done in the field of drugs and medicine are

been discussed. Now as it is known to all that Alzheimer is one of the fast growing world-

wide epidemic diseases. As it is been spreading up worldwide an ultimate cure is also

necessary for the treatment of this diseases. Now for this future prospectus a treatment is been

searching up which can be helpful in two of the major factors that are Early detection as well

as a perfect therapeutic medication of Alzheimer is. In despite of this some of the major

discoveries in medicine are also involved. The new drugs are been found up which will be

effective in curing the diseases and would be beneficial for the future point of view. It was

seen that the beta amyloid aggregates which were mainly responsible for causing the plague

in the brain which was leading to the diseases was one of the major factor. Researchers were

finding the ways in order to find out the drugs which are amyloid based which helps in

avoiding the plaque formation in the brain. As Alzheimer is an uncontrolled condition which

is to be tackling seriously and effective thing should be kept in mind. For instance:

a) Care and responsibility toward the patient is of at most importance

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b) Proper medication of drugs is also needed

c) Another factor which is of equally importance is proper scenario of the condition and

regular check-ups.

Hence these are all things which are to be seen and are necessary for the treatment in the

Alzheimer diseases.

CONCLUSION

In this review article up till now the major points which are regarding the topic i.e. A review

treatment of Alzheimer Diseases are been discussed. At last it is just said that Alzheimer is

a disease that has no cure. Until now the researchers are been trying to find out a way to

discover and find out an accurate way so as to cure the diseases. The blood plaque which is

responsible for the inability of thinking of dementia is a major problem which is too treated

first. It was also found that in order to treat and cure these amyloids plague major two steps

are: a) inhibitory drugs and b) vaccination. In this the inhibitory drugs which are been

discovered are helpful in removal of these plaques. Out of this one of the important and

effective drugs is PT32. It was seen that this drug is an enzymatic which act as a catalyst and

are required for amyloids fragments to move away from their origin of space thus reducing its

accumulation in the brain. Hence this drug proves to be quite effective. Apart from the drugs

vaccination also played one of the important steps in removal of this plaque. Out of this the

injection regarding to this is quite interesting in which the injection of beta amyloid itself is

capable of producing antibodies against the protein itself thus it helps in reducing the

accumulation of plaque.

Not only had another related treatments of this is stem cell treatment, biomarker as well as

increase or decrease in the concentration of insulin with respect to cerebrospinal fluid is also

one of the treatment of this disease. And not only this research which is going on and the

drugs which are been inventing up by the researchers is also under process and are on their

Way. Thus this term paper comprises of a brief summary about all the important points

related to the topic which is treatment on Alzheimer and all the effective way with which its

treatment can be possible not in present but in future also....

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REFERENCE-

1. Hampel H et al. The future of Alzheimer's disease: the next 10 years.

Prog Neurobiol. 2011 Dec; 95(4):718-28. doi: 10.1016/j.pneurobio.2011.11.008. Epub

2011 Nov 22.

2. 2012 Alzheimer’s diseases facts and figure Available at

Http://alzheimers.org.uk/site/scripts/documents_info.php?documentID=147

3. L. S. Schneider et.al Clinical trials and late-stage drug development for

Alzheimer's disease: an appraisal from 1984 to 2014.

4. R. Anand Kiran Dip Gill, Abbas Ali Mahdi

Therapeutics of Alzheimer's disease Past, present and future Neuropharmacology.

Volume 76, Part A, January 2014, Pages 27–50

The Synaptic Basis of Neurodegenerative Disorders 23rd Neuropharmacology

Conference

5. International Journal of Basic & Clinical Pharmacology available at

http://www.scopemed.org/?mno=46683

6. Kaj Blennow, Harald Hampel and Henrik Zetterberg

Biomarkers in Amyloid-β Immunotherapy

Trials in Alzheimer’ Disease Neuropsychopharmacology Reviews (2014) 39, 189–201;

doi:10.1038/npp.2013.154; published online 17 July 2013

7. Nicholas Kozauer, M.D., and Russell Katz, M.D

ReguN Engl J Med 2013; 368:1169-1171March 28, 2013DOI:

10.1056/NEJMp1302513latory Innovation and Drug Development for Early-Stage

Alzheimer's Diseases

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8. C Reitz, R Mayeux Alzheimer disease: Epidemiology, diagnostic criteria, risk

factors and biomarkers available at Biochemical pharmacology, 2014 -

Elsevier

9. G Chetelat nature review Aβ-independent processes rethinking preclinical AD

available at www.nature .com

10. Pohanka and Miroslav given by Alzheimer´s Disease and Oxidative Stress:

11. Bart PF Rutten and Harry WM given by Current concepts in Alzheimer’s Disease:

molecules, models and translational perspectives

12. AD Falchook, KM Heilman given by Neuroplasticity, neurotransmitters and

new directions for treatment of Alzheimer disease

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