UNIVERSITY OF

MUMBAI

ALZHEIMER’S
DISEASE
EDITED BY GUIDED BY
GULAB YADAV MRS. VIDULA
DAMLE
 INTRODUCTION
A neurodegenerative progressive cognitive deterioration
together with declining activities of daily living and
neuropsychiatric symptoms

Frontal and temporal lobes of the brain as they become

disconnected from the limbic system

Consists principally of neuronal loss or atrophy

The ultimate cause of the disease is unknown.

Genetic factors are known to be important

 HISTORY

Emil Kraepelin Alois Alzheimer

 DEMOGRAPHICS

Affect between 25–50% of individuals 85 years or older.

 Independent of sex or geographical location

Approximately 10% of people 65 years or older are at risk

for developing significant memory loss.

Approximately four in 10,000 individuals between the

ages of 40 and 60 are at risk for having Alzheimer disease.
 THEORY
1. Chemical Theories
A. Biochemical Changes in Growth Factors
B. Chemical Deficiencies
C. Toxic Chemical Excesses

2. The Genetic Theory

 A disorder can be congenital

 Several genetic markers have been identified on
chromosomes 21 and 14
 ApoE gene found on chromosome 19
Theory
3.The Autoimmune Theory
4.The Slow Virus Theory
5.The Blood Vessel Theory
 CLINICAL FEATURES

 short term memory loss

 Aphasia
 Disorientation
 Deterioration of musculature and
mobility
MILD MODERATE

SEVERE

STAGES OF
AD
 CLASSIFICATION OF
ALZHEIMER DISEASE
A) Early-onset familial Alzheimer disease
B) Late-onset familial Alzheimer disease
PATHOLOGY
 Biochemical Characteristics
 Neurochemistry
 Disease Mechanism
 Genetics Of AD
 1.Biochemical characteristics
The deposition of an abnormal protein (amyloid beta)
outside nerve cells in the form of amyloid.
Amyloid also accumulates in the walls of small blood
vessels in the brain.

Microtubules
disintegrate, collapsing
the neuron's transport
system. This may
result first in
communication
malfunctions between
neurons and later in
cell death.
2.Neurochemistry
3.Disease mechanism
Three major competing hypotheses

"Cholinergic hypothesis"
“Tau-ist" and “Ba-ptist“
 Alpha- synuclein
Signals that form memories and thoughts move through an individual nerve
cell as a tiny electrical charge.

Nerve cells connect to one another at synapses.

When a charge reaches a synapse, it may trigger release of tiny

bursts of chemicals called neurotransmitters.

The neurotransmitters travel across the synapse, carrying signals to other cells.

Alzheimer's disease disrupts both the way electrical charges travel within cells
and the activity of neurotransmitters.
 Amyloid beta

Processing of the Amyloid Precursor Protein

•Extracellular cleavage of APP by BACE releases a soluble

extracellular fragment and is followed by APP cleavage within
its transmembrane domain by γ-secretase.

•The second cleavage releases the intracellular

domain of APP and amyloid-β
 4.GENETICS OF AD
Table. Genetic of Alzheimer Disease

Chromosome Gene Mutations Consequences

21 Amyloid Single Missense Early-onset Familial
Precursor Mutations Alzheimer Disease
Protien Double missense mutaions Increases Amyloid-β
Arising of gene dosage Production
effects
14 Presenilin-1 Missense Mutations Early-onset Familial
(PS-1) Alzheimer Disease
Increases Amyloid-β
Production
1 Presenilin-2 Missense Mutations Early-onset Familial
(PS-2) Alzheimer Disease
Increases Amyloid-β
Production
19 Apolipoproti Allel-E4 Increases risk of
enE (ApoE) development of AD
 DIAGNOSIS
Detection of amyloid plaques in the brain by histopathology is the
most conclusive diagnostic tool

antibodies that bind to the particular amyloid proteins and can be

visualized by microscopic evaluation, as the antibodies are tagged
with a fluorescent or colorimetric molecule
 1 Clinical diagnosis
laboratory tests that require blood and urine or
imaging studies of the brain. By using
neuroimaging studies such as magnetic
resonance imaging (MRI) scans,
Plaques and Tangles
Beta-amyloid is chemically "sticky"
and gradually builds up into plaques.

The most damaging form of beta-

amyloid may be groups of a few
pieces rather than the plaques
themselves.

The small clumps may block cell-to-

cell signaling at synapses.
 Under the microscope

Alzheimer tissue has many fewer nerve cells and synapses than a
healthy brain.
Plaques, abnormal clusters of protein fragments, build up between

nerve cells.
Dead and dying nerve cells contain tangles, which are made up of
twisted strands of another protein.
 2 Brain Scans

 CAT scan
 PET scan
 SPECT
 MRI
 3.Genetic diagnosis
•a specific gene called APOE e4
•APP, PSEN1, and PSEN2
•APOE e4 mutation analysis can help in
diagnosing

4.Biochemical markers

A[.beta]42 accumulation in the brain is associated with reduced

levels in the cerebrospinal fluid.

Accumulation of the Tau protein in the brain is associated with

Alzheimer disease.

Therefore, increased Tau protein levels and decreased A[.beta]42 in

the cerebrospinal fluid can pinpoint
 EPIDEMIOLOGY AND PREVENTION

Risk reducers

•Intellectual stimulation
•Regular physical exercise
•Regular social interaction
•A generally healthy diet low in saturated fat
•Cholesterol-lowering drugs

Risk factors
•Advancing age
•ApoE epsilon 4 genotype (in some populations)
•Head injury
•Poor cardiovascular health (including smoking,
diabetes, hypertension, high cholesterol)
•Exposure to heavy metals
 TREATMENT

1.Acetylcholinesterase inhibitors
•Donepezil
•Galantamine
•Rivastigmine
•Tacrine

2. NMDA antagonists
•Memantine
 3.Drug Attributes

•Increase alpha-secretase activity and therefore decrease the

production of amyloid beta and beta stubs
•Increase secreted APP alpha, a potential neurotophic factor
•Increase the production of the APP intracellular domain

4.Psychosocial interventions

•Cognitive and behavioral interventions and rehabilitation strategies

•reminiscent therapy
•cognitive rehabilitation training
ALTERNATIVE TREATMENTS FOR AD
Coenzyme Q10
ubiquinone, is an antioxidant
needed for normal cell reactions to occur
idebenone,

Ginkgo biloba
•antioxidant and anti-
inflammatory properties

•to protect cell membranes,

•to regulate neurotransmitter

function.
Huperzine A
•moss extract
•a dietary supplement

Omega-3 fatty acids

•polyunsaturated fatty acid
•DHA and acid EPA.
•reduce the risk of coronary heart disease
•no more than 2 grams from supplements
•anti-inflammatory effects

Phosphatidylserine
Coral calcium
 CONCLUSION
Unfortunately, there is no cure for AD.
The goals in treating AD are to:

Slow the progression of the

disease.
Manage behavior problems,
confusion and
agitation.
Modify the home
environment.
Support family members and