Fighting

Alzheimers:
HOW NEW MEDICAL TREATMENTS COULD HELP TREAT AND
PREVENT ONSET OFALZHEIMERS

Introduction

Alzheimers Disease (AD) is a type of neurodegenerative disease

Delocalized loss of brain tissue

Currently affects 5.4 million Americans (as of 2015)

Most common type of dementia

Typically affects people 65 and up

From onset disease progresses slowly

Prognosis of 4-8 years after diagnosis

History of AD

Discovered by Dr. Alois Alzheimer

German Psychiatrist

Studied the brain a women in his

asylum

Concluded symptoms were result of

tissue loss

Spent big chunk of his life

investigating other similar cases
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Causes of AD (cont.)

Amyloid Hypothesis

Theory that amyloid-beta protein aggregates

cause atrophy of brain tissue

Amyloid-beta is a derivative of amyloid-beta

precursor protein (APP)

Changes in APP gene lead to misfolding of the

amyloid-beta protein

Amyloid-beta aggregates and becomes cytotoxic

Belief that aggregate physically damages the plasma

membrane leading to apoptosis

https://upload.wikimedia.org/wikipedia/co
mmons/b/bb/Abeta_2lfm.jpg

Causes of AD (cont.)

Tau Hypothesis

Neurofibrillary tangles within neurons are cause of AD

Normally tau helps stabilize microtubules by sticking to

tubulin molecules

In AD cells, tau is aggregated into tangles which twists

up the cytoskeleton

Ultimately leads to cell apoptosis

http://www.mybraintest.org/wpcontent/uploads/2015/09/tau-protein3.jpg

Effects on Brain anatomy

Atrophy of brain tissue in specific lobes cause

characteristic symptoms

Generally, areas of the brain more synaptically active

will be affected more

Most common areas to see tissue loss in frontal,

parietal, and temporal lobes

Frontal lobe- Loss of executive function: lack of judgment

and motivation, changes in behavior, decreased problem
solving ability

Parietal lobe Decreased ability to speak and understand

language

Temporal Lobe- Memory Loss, forgetfulness, mood swings

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pg

Treatments
CURRENT AND EMERGING

Current treatments: Cholinesterase

inhibitors
Cholinesterase Inhibitors

Loss of cognitive function is thought to be linked to damage the

Cholinergic pathways in the brain

Medications known as cholinesterase inhibitors prevent the

natural breakdown of acetylcholine

Work by binding to and inhibiting the function of Cholinesterase

Allows for more acetylcholine to be r

Current Treatments: NMDA

Inhibitors

Glutamate is produced excessively in AD patients

Glutamate is an excitatory NT

Causes action potentials to fire too often

NMDA inhibitors (Memantine) competitively bind to NDMA

receptors and prevent glutamate from binding

Excess glutamate is eventually removed from the synapse

Helps brain realize there is too much glutatmate

Current Treatments: Other

NSAIDS used to reduce inflammation

Reduced inflammation relieves pressure and lessens damage to brain

Therapy used to strengthen remaining neurons

Brain games

Memory tests

Emerging Treatments:
Aducamunab
Aducanumab is an immunoglobin known to break up amyloid-beta
aggregates

Currently being tested to destroy extracellular protein aggregates involve

in AD

Several clinical trials have been performed and showed promising results

Fig 1. Proposed mechanism for degeneration of brain tissue (Sevigny et al, 2016)

Effects of
aducanumab in ad
patients
Chart shows a notable decrease in
total amount of protein aggregates
Study not sufficient to gauge
improvement/change in cognitive
functions

Fig 2. Effects of aducamunab on AD patients (Sevigny et al, 2016). n=

number of patients assigned each dosage level.

Emerging treatments:
Aducanumabs Cousins

Solenazumab, bapineuzumab,
crenuzumab

Biologically similar proteins to

aducanumab

Are being considered as a new class of AD

medicines

Passive immunotherapy: Created outside of

body, no energy investement

In Vitro: once added to solution containing

aggregated proteins (both tau and amyloid)
they go to work on their own.

Discussion

Average lifespan is now over 70

We are seeing higher incidence of neurodegenerative disorders

Thought of losing mental function is scary

1 in every 9 people over 65 will develop AD

Much stronger drive for effective treatment for

neurodegenerative diseases in general

Researchers have been getting more funds and grants for going
into studies relating to AD and other similar diseases.

References

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no. 08-3431). Silver Spring, Md.]: Alzheimer's Disease Education & Referral (ADEAR) Center, National Institutes of Health, U.S. Dept.
of Health and Human Services.

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Bastin, C., & Salmon, E. (2014). Early neuropsychological detection of alzheimer's disease.European Journal of Clinical
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Selkoe, D. (2012). Preventing Alzheimer's Disease.Science,337(6101), 1488-1492.

Sevigny, J., et al. (2016). The antibody aducanumab reduces A plaques in Alzheimers disease. Nature 537(7618): 50-56.

Underwood, E. (2016, May 11). Tau protein-not amyloid-may be key driver of Alzheimer's symptoms. Retrieved September 23, 2016,
from http://www.sciencemag.org/news/2016/05/tau-protein-not-amyloid-may-be-key-driver-alzheimer-s-symptoms

Xiao-Ling Li, Nan Hu, Meng-Shan Tan, Jin-Tai Yu, & Lan Tan. (2014). Behavioral and Psychological Symptoms in Alzheimers
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