Lecture 8

Question 1

Alzheimer’s disease

Answer 1

• most common type of dementia
• slow, progressive neurodegeneration

Question 2

two hallmark pathologies required for a diagnosis of AD are …

Answer 2

• extracellular plaque deposits of the β-amyloid peptide
• abnormal accumulation of tau protein as neurofibrillary tangles

Question 3

symptoms of AD

Answer 3

1. Difficulty remembering recent events, may go undiagnosed for years
2. Confusion, irritability, aggression, mood swings, irritability, language problems, LTM loss
3. Loss of bodily functions
4. Death (average: 7 years post-diagnosis; < 3% survive more than 14 years post-diagnosis )

Question 4

causes of AD

Answer 4

1. Cholinergic hypothesis
2. Tau hypothesis
3. Amyloid hypothesis
4. Noradrenergic hypothesis
5. Oxidative stress hypothesis

Question 5

familial AD

Answer 5

• Usually early onset AD (<65 years)
• Autosomal dominant inheritance
• Progressive aphasia, memory loss,
  body function loss.. as late onset AD

Question 6

cholinergic hypothesis

Answer 6

• Oldest theory: postulates loss of ACh production as cause
• Basis of most current drug therapies
• But: Medications which combat ACh deficiency are not very effective!

Question 7

amyloid hypothesis

Answer 7

• Postulates beta-amyloid deposits as
  cause
• Beta-amyloid is a small piece of a larger protein called amyloid precursor protein
• Abnormal proteolysis of APP → beta
  amyloid
• Ab accumulates as extracellular plaques
  – neurotoxic?
• beta-amyloid aggregation → activate immune cells → trigger inflammation → brain cells destroyed

Question 8

tau hypothesis

Answer 8

• excessive or abnormal phosphorylation of tau results in the transformation of normal adult tau into PHF-tau (paired helical filament) and NFTs
• Tau phosphorylation decreases its capability to promote microtubule assembly, causing neurodegeneration via neuronal loss and synaptic dysfunction

Question 9

noradrenergic hypothesis

Answer 9

• Loss of noradrenergic neurons in
  locus coeruleus
• Noradrenergic system associated with psychiatric depression and psychosis
• AD also associated with depression and psychosis: is this due to noradrenalin loss?

Question 10

Parkinson’s disease

Answer 10

• slow progressive disorder
• loss of cells in substantia nigra
• less dopamine produced
• Treated with L-DOPA (dopamine precursor)

Question 11

PD symptoms

Answer 11

• tremors
• slowness
• stiffness
• balance problems

Question 12

Parkinson’s Disease
Lewy Bodies

Answer 12

Lewy body dementia is characterized by the abnormal buildup of proteins (Alpha-synuclein) into masses known as Lewy bodies

Question 13

Parkinson’s Disease
Parkin

Answer 13

• Parkin –involved in protein degradation
• Mutations cause a hereditary form of PD
• How this leads to dopaminergic
  cell death is not clear

Question 14

Dopamine Replacement Therapy

Answer 14

• Restore dopamine levels to
  restore balance
• But dopamine does not cross
  blood-brain barrier
• So we use L-DOPA (levodopa) which does
• L-DOPA converted to dopamine in body by DOPA decarboxylase
• But loses effectiveness over time

Question 15

Huntington’s disease cause

Answer 15

• Mutation in single gene: dominant, chromosome 4
• Codes for the protein huntingtin
• Huntingtin: function not clear, essential, helps regulate gene expression
• Currently no effective treatment

Question 16

huntington’s symptoms

Answer 16

• Random voluntary movements (hyperkinetic) – chorea
• Behavioural disturbances, cognitive impairment (dementia)
• Dementia
• Death 15-20 years after onset (falls, heart disease, pneumonia

Question 17

Schizophrenia - Causes

Answer 17

• Genetic factors, disruption of brain development
• Excess dopamine activity: positive symptoms? / low dopamine activity: negative symptoms?
• Environmental factors – only one of a pair of identical twins may develop schizophrenia

Question 18

Schizophrenia symptoms

Answer 18

• Extremely disturbed thinking, emotion, perception and behaviour
• Language disorganised
• Delusions, especially of persecution or grandeur
• Attention failure
• perceptual disorders
• hallucinations

Question 19

Schizophrenia - Treatment

Answer 19

• Antipsychotics – e.g. suppress dopamine receptors
• Vocational and social rehabilitation
• Antidepressants to manage associated depression
• Psycotherapy

Question 20

Classification of symptoms:

Answer 20

1. Positive symptoms: not normally present, e.g. hallucinations, delusions, disorganised thoughts
2. Negative symptoms: missing elements, e.g. absence of pleasure, lack of motivation, lack of emotion

Question 21

Creutzfeld-Jacobs Disease (CJD)

Answer 21

• neurodegenerative
• no effective tratment
• Caused by prions – infectious agents made only of protein
• Brain evelo s holes → s ong

Question 22

CJD symptoms

Answer 22

• anxiety, depression, paranoia
• progressive demntia
• death due to pneumonia
• brain cell death