Lecture 8 Flashcards
1
Q
Alzheimer’s disease
A
- most common type of dementia
- slow, progressive neurodegeneration
2
Q
two hallmark pathologies required for a diagnosis of AD are …
A
- extracellular plaque deposits of the β-amyloid peptide
- abnormal accumulation of tau protein as neurofibrillary tangles
3
Q
symptoms of AD
A
- Difficulty remembering recent events, may go undiagnosed for years
- Confusion, irritability, aggression, mood swings, irritability, language problems, LTM loss
- Loss of bodily functions
- Death (average: 7 years post-diagnosis; < 3% survive more than 14 years post-diagnosis )
4
Q
causes of AD
A
- Cholinergic hypothesis
- Tau hypothesis
- Amyloid hypothesis
- Noradrenergic hypothesis
- Oxidative stress hypothesis
5
Q
familial AD
A
- Usually early onset AD (<65 years)
- Autosomal dominant inheritance
- Progressive aphasia, memory loss,
body function loss.. as late onset AD
6
Q
cholinergic hypothesis
A
- 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!
7
Q
amyloid hypothesis
A
- 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
8
Q
tau hypothesis
A
- 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
9
Q
noradrenergic hypothesis
A
- 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?
10
Q
Parkinson’s disease
A
- slow progressive disorder
- loss of cells in substantia nigra
- less dopamine produced
- Treated with L-DOPA (dopamine precursor)
11
Q
PD symptoms
A
- tremors
- slowness
- stiffness
- balance problems
12
Q
Parkinson’s Disease
Lewy Bodies
A
Lewy body dementia is characterized by the abnormal buildup of proteins (Alpha-synuclein) into masses known as Lewy bodies
13
Q
Parkinson’s Disease
Parkin
A
- Parkin –involved in protein degradation
- Mutations cause a hereditary form of PD
- How this leads to dopaminergic
cell death is not clear
14
Q
Dopamine Replacement Therapy
A
- 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
15
Q
Huntington’s disease cause
A
- 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
