ALZHEIMER

Yovita Setiady (406138120)

Nieta Hardiyanti (406148067)
Meilisa Tiffani (406148069)

INTRODUCTION
Alzheimers disease is a
generally
a
sporadic
incurable
neuropsychiatric
condition
in
which
progressive impairment of
cognitive function occurs and
frequently accompanied by
affective
and
behavioral
disturbances.
Two
forms

OBJECTIVES
At the end of the discussion, the students
should be able to:
1.Define and characterize Alzheimer disease
2. Know its etiology and risk factors for its
development
3. Determine the structural and biochemical
changes resulting to this disease.
4. Discuss the molecular mechanism and
hypotheses in the formation of AP and NFT
5. Differentiate AP from NFT
6. Describe the imbalances of hormones/NTA
involved in this particular disease.
7. Give possible association of the following with
AD: LP, cholesterol, inflammation and immune
response, metal toxicity and free radicals and
cigarette smoking
8.Enumerate some preventive and treatment
management for AD and the rationale behind

DEFINITION OF TERMS
1. Amyloid Protein Precursor- a
trasmembrane protein
precursor
2. Apolipoprotein- a lipoprotein
which plays a role in the
movement and distribution of
cholesterol in repairing nerve
cells during development and
after injury.
3. Tau protein- tubule-associated

ETIOLOGY
- Generally of an unknown etiology
- Researchers are finding specific
biologic
factors
involved
with
Alzheimers
disease.
Various
environmental and genetic players of
appear to contribute to or trigger the
process by which these factors
destroy nerve cells leading to this
disease.

RISK FACTORS
-Age
-Gender
-Family History
-Heart
and
Disease
-Lifestyle

Vascular

GENETIC DETERMINANTS OF
AD
Late Onset
Apolipoprotein E4(ApoE4) coded from the
mutation of chromosome 19
- causes a weak a loose bonding to tau
proteins.
- causing tau to freely interact with another
molecule of tau.
- formation of paired-helical filaments
(precursor of NFT)
Increase level of ApoE4, Increase risk of
Alzheimers Disease

GENETIC DETERMINANTS OF
AD
Early Onset
APP coded from chromosome 21
Possible normal function
- May stimulate cell division and
adhesion; possible role in signaling.
- May also function as nerve protector.
- Overproduction of APP in Down
Syndrome

GENETIC DETERMINANTS OF
AD
Early Onset
- Presenilin 1 coded from chromosome 14
- Presenilin 2 coded from chromosome 1
- integral proteins
- components of proteolytic complex involve in APP
processing and degradation.
Possible normal function are:
- membrane and protein trafficking, signaling and
apoptosis.
Defective genes:
- accelerates A plaque formation.

Amyloid Precursor
Protein (APP)
Anintegral membrane protein
Concentrated in thesynapsesofneurons
Its primary function is not known, though it has
been implicated as a regulator of synapse
formation,neural plasticityand iron export
Cleaved by enzymes: ,, secretase
- Residues:
A42- Toxic amyloidogenic
A40- Nontoxic
P3- Nontoxic

Beta Amyloid (A)

A peptide of 39 42 Amino acids
Derived from transmembrane
APP
Accumulation of A fibrils leads
to formation of senile plaques in
AD

Asp Ala Glu Phe Arg His Asp

Ser Gly Tyr Glu Val His His
Glu Lys Leu Val Phe Phe Ala
Glu Asp Val Gly Ser Asp Lys
Gly Ala Ile Ile Gly Leu Met
Val Gly Gly Val Val
Ile - Ala

Tau Protein
are proteins
thatstabilizemicrotubules.
Normally phosphorylated
Increase Influx of Ca++ causes
hyperphosphorylation
Hyperphosphorylationof the tau
protein can result in theselfassemblyoftanglesof paired helical
filaments and straight filaments

Tau Hypothesis

Beta Amyloid Hypothesis

Cholinergic Hypothesis
The oldest hypothesis for AD causation.
Cholinergic hypothesis holds thata reduction in
neurotransmitter Acetylcholine is
responsible for AD.
Proposed mechanism
Evidence showsneocortical cholergic function
declines rapidly in the early stages of AD.
Decreased Acetylcholine is proposed to alter the
normal neuron signal transduction pathway,
resulting in observable histopathological changes:
Hyperphosphorylated Tau, causing neurofibrillary
tangles
Cleaving of APP into -Amyloid plaques

Hormonal Imbalance and

Neurotransmitter
Lack of Estrogen in aging women
increases the risk for A.D
Estrogen primarily blocks production of
A. It also offers anti oxidant
protection, and regulates glucose
levels in the brain
Acetylcholine decreased Ach levels in
AD is the primary reason in the
cholinergic Hypothesis

Possible Association with AD

A. Lipoproteins and Cholesterol
B. Inflammation and immune response
C. Metal Toxicity
D. Free Radicals
E. Cigarette/Tobacco Smoking

TREATMENT
NO CURE
Symptoms
Cholinesterase Drug Inhibitors
- Aricept(donezepil HCL)
- Exelon(rivastigmine)
- Razadyne(galantamine)

PREVENTION
-

Administration of NSAIDS
Calcium Channel Blocker
Statins
Dietary Intake

TERIMA KASIH

TERIMA KASIH