ALZHEIMERS

DISEASE

TINNA DEVI A/P ARMASAMY @ ARUMUGAM 012014030400

SHANTA MARIA A/P JOTHEE
012014030746
MAGESWARI A/P SUNDRARAJA
012013111216

INTRODUCTION
Dementia

Decline in memory or other thinking skills

that affects a person ability to perform
daily activities.

Damage to nerve cell in the brain(neurons)

Neurons can no long function and may die

Lead to changes in ones memory, behavior

and ability to think clearly

TYPES OF DEMENTIA

Alzheimers Disease

Vascular Dementia

Dementia with Lewy Bodies (DLB)

Frontotemporal lobar degeneration (FTLD)

Mixed Dementia

Parkinsons Disease Dementia

Creutzfeldt-Jakob disease

Normal pressure hydrocephalus

ALZHEIMERS DISEASE
(AD)

Most common neurodegenerative disease

Prevalence is increasing with the longer life span of the

human population

60-80% of dementia cases have AD

Accumulation of the protein fragment betaamyloid(plaques) outside neurons in the brain and
twisted strands of the protein tau(tangles) inside
neurons

Cause damage and death to neuron

ETIOLOGY

Genetic Mutations

Age

Family history

Apolipoprotein E (APOE) 4 Gene

Mild Cognitive Impairment(MCI)

Cardiovascular Disease Risk Factors

Social and Cognitive Engagement

Education

Traumatic Brain Injury

PATHOGENESIS
1.

2.

3.

4.

5.

AD interferes with the proper functioning of

neurons and synapses
Accumulation of protein beta-amyloid outside
neurons (plaques) & abnormal form of protein tau
inside neurons (tau tangles)
Plaques - It interferes the neuron-neuron
communication at synapses causing cell death
Tangles block the transport of nutrients and
other essential molecules causing cell death
Hence patients with AD will show brain shrinkage
from cell loss and widespread of debris from dead
and dying neurons

SYMPTOMS

Memory loss

Challenges in planning or solving problems

Difficulty in completing familiar task

Confusion with time or place

Trouble understanding visual images

New problems with speaking & writing

Misplacing things & losing the ability to retrace steps

Poor judgment

Withdrawal from work

Changes in mood & personality

DIAGNOSIS

Obtains medical & family history

Look into psychiatric history & history of

cognitive & behavioral changes

Conducts cognitive tests & physical &

neurological examinations (MRI)

Biomarkers test

PROGNOSIS

AD may begin 20 or more years before

symptoms appear

Symptoms more worsen till bed ridden

Secondary disease infection may lead to

death

TREATMENT

Pharmacologic treatment
Using medication, increase neurotransmitters in
brain

Non-pharmacologic treatment
Physical therapy

PREVENTION

Pre-clinical AD

Education

Indulging in activities that maintain healthy

brain

Continuous challenge to brain

BIOINFORMATIS IN AD STUDIES
Ayur-informatics: Establishing an in-silico-ayurvedic medication for
Alzheimers disease

Ayurveda is being seen as a rich resource for new

drug development by modern day researchers

Canscora decussata - xanthone

Ayurvedic drug for its action in CNS
For boosting memory and improving intellect
Has therapeutic effects on CNS disorders like epilepsy,
insanity & memory enhancement
Nardostachys jatamansi - nardal & Mucuna pruriens ergotamine

Mucuna pruriens

Nardostachys
jatamansi
Canscora decussata

METHODOLOGY
1.

Modeller9v7

2.

Swiss-Pdb Viewer v4.01

3.

ACD/ Chem Sketch

4.

RAMPAGE

5.

Argus Lab

6.

Hex 5.1

7.

PATCHDOCK

AD causing proteins- APP, APOE, Presenilin 1

and Presenilin 2 were taken from NCBI
entrez system

Homology modeling was carried out using

Modeller 9v7, for predicting 3 D structures

For the above mentioned proteins, homology

modeling was done using Modeller 9v7

Templates used for it were homologous protein

structures from RCBS PDB database

5 models of each of the above proteins were

generated & analyzed by Rampage
Ramchandran plot server and the best model of
each was selected

Chemical structures of active component of

each species were drawn and combined
using ACD Chem Sketch software.

This combination structure was saved as

*.mol file and was later converted to *.pdb
file using Argus lab software

RESULTS
3D structure of APP obtained by homology
modeling was analyzed by Rampage
Ramchandran plot server
Number of residues in favored
region(~98.0% expected): 381 (92.9%)
Number of residues in allowed
region(~2.0% expected): 22 (5.4%)
Number of residues in outlier region :
7(1.7%)

SUMMARY

Docking is successful and proven effective in treating

AD

This in-silico-herbal work makes use of ayurvedic

herbs in Computer Aided Drug Designing

Homology Modelling is used to model the 3D structure

of the proteins

since the work is done in in-silico platform, the

combination needs to go to clinical testing to establish
its efficacy

CONCLUSION

Hence, bioinformatics plays an important

role in drug designing for AD

It saves cost and time

Continuous research should be done to find

the cure for AD

REFERENCES
Mohini Gore*, Preenon Bagchi, Desai N.S.
and Ajit Kar in Ayur-informatics: Establishing
an in-silico-ayurvedic medication for
Alzheimers disease
Joseph Gaugler, Ph.D., Bryan James, Ph.D.,
Tricia Johnson, Ph.D., Ken Scholz, Ph.D., and
Jennifer Weuve, M.P.H., Sc.D., in the
preparation of 2014 Alzheimers Disease
Facts and Figures.