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1. Prepared by :
Mohammed A Qazzaz

2. In 1906 Dr. Alois Alzheimer was first to
describe Alzheimer's illness.
A progressive, degenerative illness that attacks
the brain and results in impaired memory,
thinking and behavior.

3. Memory loss that affects job skills.
Difficulty performing familiar tasks.
Problems with language .
Disorientation to time and place.
Poor or decreased judgment.
Problems with abstract thinking.
Misplacing things .
Changes in mood or behavior.
Changes in personality.

4. Forgetfulness .
Social withdrawal .
Hallucinations .
Seizures .
Death usually result from
malnutrition , infection ,
heart disease

5. AD is a pan ethnic , genetically heterogeneous disease
Less than 5% of patients have an early-onset familial disease ,
15-25% of patients have a late-onset familial disease and 75%
of patients have a sporadic disease .
10% of familial AD exhibits autosomal dominant inheritance ;
the reminder exhibits multifactorial inheritance .

6. Early-onset AD is a rare form of AD, affecting
only about 5 percent of all people who have
AD. It develops in people ages 30 to 60.
FAD is caused by a number of different gene
mutations on chromosomes 21, 14, and 1, and
each of these mutations causes
abnormal proteins to be formed.

7. Mutations on chromosome 21 cause the
formation of abnormal amyloid precursor
protein (APP).
A mutation on chromosome 14 causes
abnormal presenilin 1 to be made,
and a mutation on chromosome 1 leads to
abnormal presenilin 2.

8. Even if only one of these mutated genes is
inherited from a parent, the person will almost
always develop early-onset AD.
This inheritance pattern is referred to as
“autosomal dominant” inheritance.
In other words, offspring in the same generation
have a 50/50 chance of developing FAD if one of
their parents had it.

9. developing after age 60. genetics of AD have found that
the mutations seen in early-onset AD are not involved in
this form of the disease.
Both familial AD and sporadic late-onset AD are strongly
associated with Apo lipoprotein E (APOE) gene found on
chromosome 19
APOE comes in several different forms, or alleles. Three
forms—APOE ε2, APOE ε3, and APOE ε4—occur most
frequently.

10. APOE ε4 occurs in about 40 percent of all people who
develop late-onset AD.
and is present in about 25 to 30 percent of the
population. People with AD are more likely to have an
APOE ε4 allele than people who do not develop AD.
However, many people with AD do not have an APOE
ε4 allele.

11. APP undergoes endoproteolytic cleavage in the to
produce a peptide of 40 amino acid
(Aβ40) the function of Aβ40 is unknown .
In contrast , cleavage of APP in the endoplasmic
reticulum produce a peptide of 42 or 43
Amino acid (Aβ42/ Aβ43) .and its neurotoxic
substance .

12. Patients with AD have a significant increase in
(Aβ42/ Aβ43) aggregates within the brain
Mutation in APP PSEN1 and PSEN2 increase the
production of (Aβ42/43) .
1% of all AD cases occur in patients with down
syndrome . Who overexpress APP.
The role of ε4 is unclear .

13. Cortical atrophy .
Neurodegeneration in cholinergic neurons of hippocampus .
Extracellular neuritic plaques .
Intraneuronal neurofibrillary tangles .
Amyloid deposits in the wall of cerebral arteries .

14. An AD plaque An AD tangle

15. Beta-amyloid Plaques
Amyloid precursor protein (APP) is the
precursor to amyloid plaque.
1. APP sticks through the neuron
membrane.
2. Enzymes cut the APP into
fragments of protein, including beta-
amyloid.
3. Beta-amyloid fragments come
together in clumps to form plaques.

17. Mutation in PSEN1 are fully penetrant and usually cause rapidly
progressive disease with mean onset at 45 .
Mutation in APP are fully penetrant and usually cause a rate of AD
progression similar to that of late-onset AD with range onset of 45
to 75 .
Mutation in PSEN2 are not fully penetrant and usually cause
slowly progressive disease with onset ranging from 40 to 57 .

18. Increase the cholinergic activity
•cholesterol-lowering drugs
•anti-oxidants (vitamins) and folic
acid
•anti-inflammatory drugs
•substances that prevent formation
of beta-amyloid plaques
•nerve growth factor to keep
neurons healthy

19. Old age
Family history
Female gender
Down syndrome