Alzheimer's disease

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. AloisAlzheimer

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 → βamyloid (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 βis 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& γSecretase)
•α-Secretase activity give rise to soluble form of APP which
do not lead to plaque formation but
β& γSecretase when act togetherly on APP they form
Amyloid βfragments which further give rise to plaques.
•Gene for APP is present on 21
st
chromosome . Mutations in
this gene results in increased formation of Aβ.

13. ApoE allele & AD
Gene for Apolipoprotein E → on 19
th
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 βin
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 –7
th
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