neurodegenerative diseases

Question 1

What are neurodegenerative disorders?

Answer 1

• gradual dysfunction of neurons over time eventually leading to death of neurons
• usually progressive dysfunction

Question 2

What is dementia?

Answer 2

• significant loss of intellectual abilities including cognition, memory capacity, concentration & judgement
• can be severe enough to interfere with social or occupational function
• gets progressively worse over time

Question 3

What anatomical changes happen to the brain during alzeimers disease?

Answer 3

• severe cortical shrinkage
• severly enlarged ventricles
• severe shrinkage of hippocampus

Question 4

what is the leading cause of dementia?

Answer 4

Alzheimer’s disease - a neurodegenerative disorder

Question 5

What are the main 2 hallmarks of Alzheimer’s disease?

Answer 5

• amyloid plaques
• neurofibrillary tangles

Question 6

What are amyloid beta plaques?

Answer 6

• extracellular deposits of the amyloid beta protein

Question 7

What are neurofibrillary tangles?

Answer 7

• insoluble fibers found in neurons
• consist of an abnormally phosphorylated protein called Tau
• note that tau is important for microtuble transport
• therefore the disease causes the microtubule within the neurons collapse and cause cell death

Question 8

What are neurofibrillary tangles associated with?

Answer 8

• loss of neurons and synapses, brain atrophy ( wastage) & ventricle enlargement

Question 9

Discuss the role of Tau with microtubules- what are mt’s.. how does tau bind and what happens with disorders

Answer 9

• microtubules represent tracks for fast axonal distribution of cellular organelles
• Tau binds and stabilizes the mt’s
• dephosphorylation by phosphatase enzymes strengthens the affinity of Tau for microtubules
• phosphorylation of certian enzymes inhibit the binding of tau to microtubules which leads to depolymerisation of them
• UNBOUND, ABNORMALLY PHOSPHORYLATED Tau aggregates into paired filaments

Question 10

What is alpha beta?

Answer 10

• fragment of a larger protein called the amyloid precursor protein APP

Question 11

What is APP? - also mention its role in AD

Answer 11

• membrane bound protein which is expressed under normal conditions and is involved in neural growth and repair
• cleavage of APP in AD which causes pathophysiological accumulation - forms hard insoluble plaques between nerve cells

Question 12

What is the cleavage of APP mediated by?

Answer 12

• mediated by a family of enzymes called secretase enzymes

Question 13

Describe the non amyloidogenic pathway of cleaving APP

Answer 13

• alpha secretase cleaves within the APP fragment to produce APPsa
• gamma secretase cleaves APPsa to produce p3 fragment P3 fragments can be found in amyloid plaques

Question 14

Describe the amyloidogenic pathway in APP cleavage

Answer 14

• step 1: beta secretase cleaves APP at the amino terminus of the alpha- beta peptide . This releases APP-s beta
• step 2: gamma secretase cleaves APPs Beta to produce the full length alpha beta peptide
• alpha beta fragments aggregate extracellularly to cause plaques

Question 15

What is familial Alzheimer’s disease?

Answer 15

• genetic component
• often associated with mutations in the APP gene or mutations in the enzymatic components of the secretase family of proteins
• autosomal dominant inheritance
  -rare

Question 16

What is sporadic Alzheimer’s disease?

Answer 16

• cause is still unknown
• 90% of cases
• age is largest risk factor - 65 and older
• other risk factors : history of traumatic injury to the brain

Question 17

How can Alzheimer’s be treated? 1 way

Answer 17

• acetylcholinesterase inhibitors
• loss of cholinergic transmission and Ach synthesizing neurons in subcortical nuclei of the forebrain
• improves cognition, behavior and functional ability BUT only in apporx 20% of patients

Question 18

How can AD be treated ? way 2

Answer 18

• NMDA receptor antagonists / partial antagonists
• these address the problem of inappropriate glutamate/NMDA receptor over activation

Question 19

what are mild symptoms in Alzheimer’s disease?

Answer 19

-confusion and memory loss
-personality changes
-judgement problems
difficulty w/ routine tasks

Question 20

what are examples of moderate symptoms associated with Alzheimer’s disease?

Answer 20

-difficulty w/ personal care eg bathing and dressing
-anxiety
-insomnia or sleep disturbances
-wandering and pacing
-trouble with recognising familiar faces

Question 21

what are examples of severe symptoms associated with Alzheimer’s disease?

Answer 21

-loss of speech
-loss of appetite
-loss of bladder and bowel control
-complete dependence on caregiver

Question 22

what is cretutzfeld jakobs disease?

Answer 22

• a prion disease
• an abnormal protein In the brain triggers the folding of normal proteins in the brain
  -untreatable and fatal

Question 23

what are examples of symptoms of CJD?

Answer 23

• loss of memory
  -mood changes
  -clumsiness
  -jerky movements

Question 24

what are the 3 different types of CJD?

Answer 24

-acquired
-sporadic CJD - cause unknown - affects adults > 50 yrs
-variant CJD - new type - affects young people

Question 25

what is hungtinton’s disease?

Answer 25

-hereditary neurodegenerative disorder
-caused by a mutation in the HPP gene which leads to the abnormal production of the hungtinton protein
-degeneration of GABAergic neurons In striatum