Alzheimer’s disease and
Dementia is a symptom
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
An irreversible, progressive brain disease that slowly
destroys cognitive functions.
Gradual impairment of higher intellectual functions.
Severe Cortical dysfunction → Memory loss &
In 10-15 years, patient becomes profoundly
disabled, mute & immobile.
• First case studied in 1906 by German
Psychiatrist and neuropathologist Alois
• Most cases are Sporadic
5-10 % are Familial.
• Diagnosed in people over 65 yrs of
• Scientists estimate that around 4.5
million people now have AD.
Dr. Alois Alzheimer
Macroscopic examination of Brain shows :
• Cortical Atrophy
• Widening of cerebral sulci
• Ventricular enlargement
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
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
Pathogenesis and Molecular
• Amyloid β is critical molecule in pathogenesis of AD.
• It is derived through processing of Amyloid Precurssor
• 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.
ApoE allele & AD
Gene for Apolipoprotein E → on 19th chromosome.
In humans, there are three alleles of this gene encoding
ApoE2 ApoE3 ApoE4
People with ApoE4 allele show larger content of Amyloid β in
• 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
AD is diagnosed from :
Collateral history from relatives
Clinical & pathologic features
Advanced imaging techniques
Computed tomography (CT)
Magnetic Resonance Imaging
Positron Emission tomography
Pathologic Basis of Disease – 7th edition -
by Kumar, Abbas, Fausto.
Lehninger Principles of Biochemistry, 5th edition -
David L. Nelson, Michael M. Cox