Alzheimer's Disease

Question 1

What are the symptoms of Alzheimers disease?

Answer 1

• Memory Loss [Short term ONLY], unable to learn, confusion, messy, anxiety, suspicion [wont recognize themself], hallucinations, motor dyfunctions

Question 2

What are some of the environmental risk factors associated with Alzheimers disease?

Answer 2

• Age, Low education levels, reduced mental and phyiscal activity, head injury

Question 3

What is the neuropathology of Alzheimers disease?

Answer 3

• Loss of brain volume
• Formation of the Amyloid Plaques [Extracellular] and the Neurofibrillary Tangles [Intracellular] = Destruction of the Synapse

Question 4

How are amyloid beta [Ab] peptides formed?

Answer 4

• Normal Cleavage: a-secretase breaks Ab in the middle = non-toxic pieces
• Abnormal Cleavage: b- and y-secretase that breaks Ab at both ends releasing Ab into extracellular space = making the plaques

Question 5

How long is a Ab residues typically?

Answer 5

• Ab is about 40 to 42 residues longs with Ab42 being the most common; making more plaques

Question 6

What is the way that Ab is able to make Tau Tangles?

Answer 6

• With the excess of the Ab plaques, that activates kinases [GSK3b; CDK5] causing the phosphorylation of the TAU fibers, making them tangle and fall off the tubules = DECREASING cognition

Question 7

What are the effects of Ab on the Mircoglial cells and its activation ?

Answer 7

• Ab will cause the microglial cells to activate, initiating the immune response releasing cytokines, which will damage the cells of the brain = Neuroinflammation; these damages parts will then reactivate the microglial cells [basically repeats the process]

Question 8

What is the impact of ApoE genetics on the risk of Alzheimers disease?

Answer 8

• ApoE: responsable to transporting cholesterol in the brain
• There are 3 type; ApoE-2, ApoE-3, ApoE-4
• Having 1 or 2 ApoE-4 genes = Increase risk of AD

Question 9

What are some of the therapies that are used in treating Alzheimers Disease?

Answer 9

• Cholinesterase Inhibitors, Anti-Gluatmatergic,

Question 10

What are the cholinesterase inhibitors used in Alzheimers Disease?

Answer 10

• Donepezil, Rivastigmine, Galantamine

Question 11

What is the function of cholinesterase inhibitor in alzheimers disease?

Answer 11

• Blocks the cholinergic receptor allowing it to compensate for the loss of acetylcholine
• Inhibits that breakdown of acetylcholine within the brain, allowing it to resolve some of the cognitive and behavioral issues

Question 12

How do Donepezil, Rivastigmine, and Galantamine affect the acetylcholinesterase?

Answer 12

• Donepezil: Specefic; Reversible Inhibitor of acetylcholinestase
• Rivastigmine: Inhibits both acetylcholinesterase and butyrylcholinesterase
• Galantamine: Selective; Reversible inhibitor of acetylcholinesterase and enhances the action of acetylcholine on NIC receptors

Question 13

What is the anti-glutamatergic therapy used in Alzheimers disease?

Answer 13

• Memantine: NMDA Antagonist that blocks the glutamatergic neurotransmission
• Glutamate: excitatory neurotransmitter that is involved in learning and memory; too much can cause neuronal death = DECREASING learning and memory

Question 14

What are some of the new strategies that are used for disease modifying therapy for alzhemiers?

Answer 14

• Ab Generation [b- and y-secretase inhibitors]
• Ab Aggregation [Inositol, Polyphenols, Peptides]
• Ab Clearence [Vaccines, Aducanumab]
• Tau Kinase Inhibitors [Lithium, Valproate]
• Glutamate-Mediated Excitotoxicity [Troriluzole]
• Inflammation or Oxidative Stress [NSAIDS]

Question 15

What is the purpose of Florbetapir (18F) in Alzheimers Disease?

Answer 15

• Helps with the imaging of Amyloid beta and allow us to treat the disease better.
• 18F-Flortaucipir: looks at the Tau Tangles