Alzheimer’s Disease

What is Alzheimer’s disease Incidence & PrevalenceSigns & SymptomsCausesMechanismsDiagnosisTreatment & Management

Outline

Neurodegenerative dementia causing memory loss & cognitive decline.

Cause shrinkage of the brain.

Discovered by German psychiatrist & neuro-pathologist Alois Alzheimer in 1906.

Most common cause of dementia in adults.

Introduction

Mostly diagnosed in people over 65 years of age

(Late-onset Alzheimer’s disease).

Early-onset AD may occur within 30-60 years.

In 2006, throughout the world 26.6 million

people were affected.

Within 2050, among 85 people, 1 will be affected

globally.

Statistics of AD

Memory loss.Difficulty performing familiar tasks.Problems with language.Disorientation to time & space.Poor/decreased judgment.Problems with abstract thinking.Misplacing things.Changes in mood & behavior.Changes in personality.Loss of initiative.

Signs & Symptoms

1. Genetic cause

2. Cholinergic hypothesis

3. Amyloid hypothesis

4. Tau hypothesis

5. Others

Causes

Genetic Cause:

Involvement of Amyloid precursor protein(APP),

Presenilin 1 & Presenilin 2.

Carrying APOEε4 causes 40-80% of Late-onset AD.

Other genes responsible for causing AD are-

CLU, PICALM, CR1, BIN1, MS4A, ABCA7, EPHA1, CD33,

CD2AP, ATP5H, EXOC4, CTNA3, RNF219, TREM2 etc.

Causes

Cholinergic Hypothesis:

Reduced synthesis of neurotransmitter ,

acetylcholin.

Large scale aggregation of amyloids.

Results in neuroinflammation & degeneration

of neurons.

Causes

Amyloid Hypothesis:

Deposition of β-Amyloid proteins.

APP present on chromosome 21 together with

Down syndrome causes 90% of Early-onset AD.

N-APP triggers self destruct pathway by binding

to a neuronal receptor, Death Receptor 6 (DR6).

Causes

Tau Hypothesis:

Degeneration of tau proteins.

Formation of neurofibrillary tangles.

Initiation of AD.

Causes

Others:

Involvement of Herpes simplex virus carrying

susceptible version of apoE gene.

Oxidative stress in brain.

Dys-hemostasis of bio metal metabolism.

Causes

Formation of β-Amyloid plaques:

Normally, α-secretase produces APP & γ-secretase

creates another shorter version of APP which is then

degraded.

In case of AD, β-secretase together with γ-secretase

produces longer, sticky form of β-amyloid proteins (Aβ).

Accumulation of Aβ proteins produce senile plaques.

Mechanism

Enzymes act on the APP (amyloid precursor protein) and cut it into fragments. The beta-amyloid fragment is crucial in

the formation of senile plaques in AD.

Formation of Neurofibrillary Tangles:

In neurons, signal transduction occurs through

microtubules which are stabilized by tau proteins.

In AD, tau proteins are degenerated.

& causes microtubules to disintegrate.

Leads to formation of neurofibrillary

tangles of tau proteins.

Causes neuron degeneration.

Mechanism

http://upload.wikimedia.org/wikipedia/commons/5/51/TANGLES_HIGH.jpg

Based on patient’s history, relatives’ history & observation of his behavior.

Assessment of intellectual functioning by memory tests.

Exclusion of other cerebral pathology of dementia using-

Computed tomography (CT) Magnetic resonance imaging (MRI) Single photon emission computed

tomography (SPECT)Positron emission tomography (PET)

Diagnosis

.

No known treatment found yet as, death of brain cells can’t be halted or reversed.

Some therapeutic drugs are available that can help a patient to live ably. Those includes-

• Donepezil• Alantamine• Rivastigmine• Tacrine• Menantine etc.

Treatment & Management

Some potential treatment may involve-Application of chaperone molecules.Gene therapy in reversing memory loss.Application of Dab2 protein, which exhibits

neuroprotective effects.Regulation of TGF- β1/SMAD signaling.

Most important thing an AD patient needs is proper nursing & care.

Treatment & Management

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