AD

1. Etiopathogenesis of Alzheimer's
disease

2. Introduction
• Alzheimer’s is the most common cause of
dementia in adult life and is associated with
the selective damage of brain regions and
neural circuits critical for memory and
cognition.
• The pathogenesis of this disease is complex,
and involves many molecular, cellular, and
physiological pathologies.

3. What is AD?
• Alzheimer’s disease (AD) is a devastating
illness characterized by progressive memory
loss, impaired thinking, personality change,
and inability to perform routine tasks of daily
living.

4. To understand Alzheimer’s disease, it’s
important to know a bit about the
brain…

5. Cells of the nervous system
1. Neurons
2.Neuroglia cells
Astrocyte
Oligodentrocytes
Ependymal cells
Microglia

6. Neurons
• The brain has billions of neurons, each with an
axon and many dendrites.
• To stay healthy, neurons must communicate
with each other, carry out metabolism, and
repair themselves.
• AD disrupts all three of these essential jobs.

7. Structure of the neuron

9. Etiology and risk factors
• Although the risk of developing AD increases
with age – in most people with AD, symptoms
first appear after age 60 – AD is not a part of
normal aging. It is caused by a fatal disease
that affects the brain.
• Family history

11. CERBRAL HEMCCCCCCCERISPHERES

13. THE BRAIN STEM

15. Other crucial parts….
• Hippocampus: where short-term memories
are converted to long-term memories
• Thalamus: receives sensory and limbic
information and sends to cerebral cortex
• Hypothalamus: monitors certain activities and
controls body’s internal clock
• Limbic system: controls emotions and
instinctive behavior (includes the
hippocampus and parts of the cortex)

16. Etiology for AD
Unknown
Aging
Familial cause

17. AD and brain
• Amyloid plaques
• Neuro fibrillary tangles
• Loss of connection between cells and cell
death
• Genetic factor
• Cellular and other cause

18. Amyloid plaque
 Amyloid precursor protein (APP) is the
precursor to amyloid plaque.
 APP sticks through the neuron membrane.

19. Contd….
 Enzymes cut the APP into fragments of
protein, including beta-amyloid.

20. Contd…
• Beta-amyloid fragments come together in
clumps to form plaques.

21. Contd..
• In AD, many of these clumps form, disrupting
the work of neurons. This affects the
hippocampus and other areas of the cerebral
cortex.

22. NORMAL AND AD CEREBRAL CORTEX

23. Neurofibrillary tangles
• Neurons have an internal support structure
partly made up of microtubules. A protein
called tau helps stabilize microtubules.
• In AD, tau changes, causing microtubules to
twist together in helical fashion , and tau
proteins clump together to form
neurofibrillary tangles.

24. NEURO FIBRILLARY TANGLES

26. Genetic factor
• Presenillin -1 and 2 genes are muted to cause
over production of betaamyloid(cell
damage/death/inflammation)
• Apolipoprotein E (ApoE) gene on chromosome
19
• Four allele of apolipoprotein –E that is Apo E-
2,3,4.
• Role in cholesterol transport
• E4 associated with AD but E2 is protective

27. Contd....
– ApoE4 promotes the formation of neuritic
plaques;also binds to beta-amyloid to make it
insoluble.
-Apo E-4 increase the risk of person to develop
late onset of AD
– E4 neither necessary nor sufficient to cause AD
(many people have apoE4 gene, but do not
have AD).

28. Cellular and others ….
• Aging causes formation of free radicals
• HT, obesity, smoking, atherosclerosis, high
cholesterol and homocysteine increase the
risk of AD.

29. Conclusion
The neural damage in AD is irreversible, and
hence the disease cannot be cured.
There is no effective drug for relieving
symptoms, and no prospect of one in the near
future.