Brain Bee Chapter 15: Neurodegenerative Diseases

What do Neurodegenerative Diseases involve?

Involve progressive destruction of nerve cells, and they mostly affect older people

Recent studies show that Neurodegenerative Diseases involve what?

Recent studies show that these diseases may involve misfolded proteins called prions

What are Prions?

• Prions are proteins whose normal 3D structure is altered, so they stop functioning correctly. 

• Misfolded proteins can damage nerve cell

What is Alzheimers?

A type of dementia that is eventually fatal.  It causes the brain to go through irreversible degeneration which leads to memory and reasoning problems

What are the symptoms of Alzheimer's disease in Early stage?

Memory problems, difficulty concentrating, confusion about time or place

What are the symptoms of Alzheimer's disease in Mild stage?

Changes in personality and behavior, lost, repeating questions, misplacing objects

What are the symptoms of Alzheimer's disease in Moderate stage?

Difficulty recognizing family and friends, can’t learn, hallucinations, difficulty completing multi-step tasks

What are the symptoms of Alzheimer's disease in Severe stage?

Body begins to shut down, completely dependant on others, limited communications, wight loss seizures, skin infections

What are the two main biomarkers in Alzheimer's?

Amyloid-beta and Tau Protein

What are the characteristic functions of Amyloid-beta?

In Alzheimer's, Amyloid-beta forms plaques outside neurons which are abnormal clumps of protein fragments

What are the characteristic functions of Tau Protein?

In Alzheimer's, Tau Protein forms neurofibrillary tangles inside neurons

What is a new method of Neuroimaging to find biomarkers?

Using a tracer that attaches to amyloid plaques and shows their location

What are the causes and pathology of Alzheimer's disease?

Causes are not fully understood but most cases are likely genetics, environment, and lifestyle habits, Head trauma may contribute

What are the first changes in Alzheimer's disease?

• There is early damage in the neuronal transport system

• Patients produce less neurotransmitters

• Over time, axons and synapses are destroyed

What is the two main suspected causes of the bodily changes of early Alzheimer's disease?

Neuritic Plaques and Neurofibrillary Tangles

What are the characteristic functions of Neuritic Plaques?

Made out of amyloid-beta

What two forms can Amyloid-beta take?

• Soluble: Damages synapses and highly toxic

• Insoluble: Less toxic but builds up a lot

What is the Amyloid Hypothesis?

The amyloid hypothesis suggests that the amyloid-beta buildup starts a chain reaction that leads to the disease

What are Neurofibrillary Tangles?

When Tau proteins become abnormal

Early-Onset Alzheimer's is caused by what mutations?

Early-onset Alzheimer's is a caused by mutations in three genes: APP, PSEN1 and PSEN2

What mutation is a big risk factor for late-onset Alzheimer's?

The ApoE4 variant of the APOE gene is a major risk factor but does not guarantee the disease

What are treatments for Alzheimer’s disease?

Cholinesterase Inhibitors, NMDA receptor antagonist,  A combination of Donepezil and Memantine

What are the characteristic functions of Cholinesterase Inhibitors? Give some examples:

Acetylcholinesterase is an enzyme that breaks down acetylcholine (a neurotransmitter involved in memory). Cholinesterase Inhibitors block that enzyme to counteract the loss caused by Alzheimer's 

• 1. Donepezil: For all stages

• 2. Galantamine: Mild to moderate 

• 3. Rivastigmine: for all stages

What are the characteristic functions of NMDA receptor antagonists? Give some examples.

Too much calcium damages neurons, so Memantine blocks excess calcium

• 4. Memantine

What are the characteristic functions of a combination of Donepezil and Memantine?

For moderate to severe Alzheimer's

What is Parkinson’s Disease?

Parkinson’s disease is the second most common neurodegenerative disorder, after Alzheimer’s

What are Symptoms of Parkinson’s disease?

Slow movement, muscle stiffness, poor coordination, resting tremor

What causes Parkinsons?

Parkinson’s is caused by the loss of dopamine producing neurons in the substantia nigra

What causes the neuron death in Parkinsons?

This neuron death is caused by mitochondrial damage

What are Genetic Factors in Parkinsons?

• Early-onset Parkinsonism can be caused by a mutation in the PARK2 gene

What protein structures are seen in Parkinson’s?

Abnormal protein clumps called Lewy bodies are seen in Parkinson's

What are some treatments for Parkinson’s?

• Levodopa: Temporarily relieves some symptoms but doesn’t slow disease progression

• Deep Brain Simulation

• Experimental treatment to to see if high pressure can break Lewy bodies

What is ALS?

Amyotrophic Lateral Sclerosis

What are the characteristic functions of ALS?

ALS is a progressive and fatal disease that destroys motor neurons, it causes muscle weakness, loss of movement control, and eventually death

What are early symptoms of ALS?

Causes muscle weakness, loss of movement control, and eventually death

What are symptoms of later ALS?

Weakness spreads to other muscles, loss of ability to move, speak and eat, respiratory muscles weaken which leads to death

What is the cause of ALS?

Motor neurons connect the brain and the spinal cord to voluntary muscles, so when motor neurons die, muscles weaken twitch and atrophy (shrink)

There are two different ALS? What are they?

• Genetic ALS (also called Familial ALS): Caused solely by Genetics

• Sporadic ALS: No clear inheritance patterns

What are genes related to ALS?

C9ORF72, SOD1

What are current treatments for ALS?

Edaravone: 

• An antioxidant, it can ease symptoms

Riluzole:

• Lowers glutamate levels and extends life by a few months

What is Huntington’s Disease?

Huntington’s is a heritable neurodegenerative disease which impairs voluntary movement and cognition

What causes Huntington’s Disease?

HD is caused by a mutation in the HTT gene on chromosome 4, which codes for the huntingtin protein.

What are the symptoms of early Huntington’s Disease?

Irritability, mood swings, depression

What are the symptoms of progressive Huntington’s Disease?

• Difficulty walking, speaking, swallowing

• Worsening thinking and reasoning abilities

What are the symptoms of JuvenileHuntington’s Disease?

• Slow movements, clumsiness, frequent falls, rigidity

• Slurred speech, drooling

• Seizures

What is the genetic mutation on the HTT gene in Huntingtons disease? Normally, the HTT gene helps with what?

Genetic Mutation: Normally, CAG is repeated 10-15 times in the gene, but the HD mutation causes there to be 36-120+ repeats

Normally this protein helps with cell signaling, transport, protein binding and protecting cells from self-destruction

What effect on cells does the mutated Huntington’s protein have?

Mutated Huntington protein clumps together and disrupts mitochondria. Then neurons stop working together and there is cell death

What are treatments for Huntingtons?

• Gene Silencing Treatments

• Symptom management

• Biomarkers for Detection