Brief Information about Alzheimer's Disease

1. - Kalpesh Anil Zunjarrao
Alzheimer’s Disease

2. Difference between
Alzheimer’s disease and
Dementia ?
Dementia is a symptom
and
Alzheimer’s disease is the cause of the symptom
Patient can have a form of dementia that is
completely unrelated to Alzheimer’s disease

3. What is Alzheimer’s
disease ?
An irreversible, progressive brain disease that slowly
destroys cognitive functions.
Gradual impairment of higher intellectual functions.
Severe Cortical dysfunction → Memory loss &
Aphasia.
In 10-15 years, patient becomes profoundly
disabled, mute & immobile.

4. Introduction
• First case studied in 1906 by German
Psychiatrist and neuropathologist Alois
Alzheimer.
• Most cases are Sporadic
5-10 % are Familial.
• Diagnosed in people over 65 yrs of
age.
• Scientists estimate that around 4.5
million people now have AD.
Dr. Alois Alzheimer

5. Morphology
Macroscopic examination of Brain shows :
• Cortical Atrophy
• Widening of cerebral sulci
• Ventricular enlargement

6. Entorhinal cortex Hippocampus Neocortex
Pathologic changes :

7. Preclinical AD Mid / moderate AD
Severe AD

8. Major microscopic abnormalities :
• Neuritic plaques
• Neurofibrillary tangles

9. Neuritic plaques
 Spherical collections of dilated, twisted neuritic processes
around the central core
 20 – 200 μm
 Periphery → Microglial cells & Astrocyts
 Central core → β amyloid (Aβ)
peptide,Cytokines, Complement cascade, Apolipoprotiens

10. Neurofibrillary tangles
 Bundles of filaments in cytoplasm which displace or
encircle the nucleus.
 Commonly found in cortical neurons in entorhinal
cortex, hippocampus & basal fore brain.
 Insoluble & resistant to clearance.
 They are made up of paired
helical filaments of
hyperphosphorylated ‘tau’
protein.

12. Pathogenesis and Molecular
Genetics
• Amyloid β is critical molecule in pathogenesis of AD.
• It is derived through processing of Amyloid Precurssor
Protein.
• APP : transmembrane protein & it has cleavage sites for 3
enzymes (α,β & γ Secretase)
• α-Secretase activity give rise to soluble form of APP which
do not lead to plaque formation but
β & γ Secretase when act togetherly on APP they form
Amyloid β fragments which further give rise to plaques.
• Gene for APP is present on 21st chromosome . Mutations in
this gene results in increased formation of Aβ.

13. ApoE allele & AD
 Gene for Apolipoprotein E → on 19th chromosome.
 In humans, there are three alleles of this gene encoding
Apolipoprotein E.
ApoE
ApoE2 ApoE3 ApoE4
 People with ApoE4 allele show larger content of Amyloid β in
their brain.

14. Clinical features
• Memory loss & forgetfulness
• Difficulty in performing familiar tasks
• Problems with language
• Disorientation to time or place
• Poor or decreased judgment
• Problems with abstract thinking
• Misplacing things
• Changes in mood or behavior
• In severe stage patient becomes mute
& immobile

15. Diagnosis
AD is diagnosed from :
 Patient’s history
 Collateral history from relatives
 Clinical & pathologic features
Advanced imaging techniques
used :
 Computed tomography (CT)
 Magnetic Resonance Imaging
(MRI)
 Positron Emission tomography
(PET)

16. Prognosis
No Cure !!!

17. BIBLIOGRAPHY
Books
Pathologic Basis of Disease – 7th edition -
by Kumar, Abbas, Fausto.
Lehninger Principles of Biochemistry, 5th edition -
David L. Nelson, Michael M. Cox
Websites
http://en.wikipedia.org/wiki/Alzheimer's_disease
http://www.dementiaguide.com/community/dementia-
articles/Difference_Alzheimer's_and_Dementia

18. Thank You !
Created by - Kalpesh