- Kalpesh Anil Zunjarrao

Alzheimer’s Disease

Difference between Alzheimer’s disease

and Dementia ?

Dementia is a symptomand

Alzheimer’s disease is the cause of the symptom

Patient can have a form of dementia that is completely unrelated to Alzheimer’s disease

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.

Introduction

• First case studied in 1906 by German Psychiatrist and neuropathologist Alois Alzheimer.

• Most cases are Sporadic5-10 % are Familial.

• Diagnosed in people over 65 yrs of age.

• Scientists estimate that around 4.5 million people now have AD.

Dr. Alois Alzheimer

MorphologyMacroscopic examination of Brain shows :• Cortical Atrophy• Widening of cerebral sulci• Ventricular enlargement

Entorhinal cortex Hippocampus Neocortex

Pathologic changes :

Preclinical AD Mid / moderate AD

Severe AD

Major microscopic abnormalities :

• Neuritic plaques

• Neurofibrillary tangles

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

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.

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 butβ & 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.

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.

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

DiagnosisAD 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)

PrognosisNo Cure !!!

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

Thank You !

Created by -

Kalpesh