Alzeihemers

Question 1

popular neurodegenerative diseases (NDD)

Answer 1

Alzeiheimer
Dementia
Parkinson’s
motor neuron disease
Huntington disease

Question 2

NDD based on anatomic structure

Answer 2

-Frontotemporal dementia
-Extrapyramidal disorder
-Spinocerebella ataxia
-Spinal muscular atrophy

Question 3

Principle molecular abnormality in NDD

Answer 3

Dysregulation of synuclein
Amyloid processing

Question 4

NDD causes

Answer 4

Combination of genetic and environmental factors
-greatest risk factor is age
-Inherited disorders
-long term exposure to pesticides, toxins and chemicals have been linked to parkinsons

Question 5

Main problem of NDD

Answer 5

-Not curable
-Leads to problems in movement (ataxia), mental functioning (dementia) and affect a person’s ability to move, speak and breath

Question 6

Alzeihemers (AD) demographic

Answer 6

60-70% of all dementia cases
one in every 68 individuals
SA= 850 000 cases

Question 7

Parkinsons demographic

Answer 7

1 in 5000-10,000

Question 8

Huntington disease demograph

Answer 8

1 in 10,000-20,000

Question 9

Summary of neurodegenerative diseases

Answer 9

Insert

Question 10

AD definition

Answer 10

It is characterised by the presence of extracellular amyloid plaques and intracellular neurofibrillary tangles, resulting in neuronal dysfunction and apoptosis

Question 11

APP

Answer 11

Amyloid precursor protein

Question 12

Normal treatment of APP

Answer 12

APP undergoes proteolytic processiing, cleaved by alpha-secretase to generate soluble peptide sAPP(alpha=a) and a C83 carboxy-terminal fragment resulting in an integral membrane protein that is activated
-APP is inactive

Question 13

function of sAPPa

Answer 13

-Associated with normal synaptic signalling
-Regulates processes like neuronal survival and synaptic platicity that contribute to higher-order brain functions like learning, memory and other behaviours

Question 14

Problem with APP processing

Answer 14

Mutations lead to formation of B-secretase and gamma-secretase which cleave APP to release extracellular monomers of varying sizes, the most signifcant Amyloid Beta-peptide 1-40/42 (ABeta40/42)

Question 15

Effects of Abeta

Answer 15

-The APP imbalance increases neurotoxic aggregation, yielding Abeta oligomerisation and plaque formation
-ABeta aggregation leads to blocked ion channels, disruption of calcum homeostasis and mitochondrial oxidative stress
-Impaired energy metabolism and abnormal glucose processing
-Alters synaptic functioning which leads to cell death

Question 16

cells affected by Ab

Answer 16

Glial cell types like astrocytes and microglia are affected
-Glial cells play an NB role to protect neuronal environment

Question 17

Overall effect of Ab

Answer 17

accumulation of amyloid monomers, oligomers and plaque affects neuronal and glial cells which results in vulnerable neurons and cell death

Question 18

Neurofibrillary tangles

Answer 18

-Composed of hyperphosphorylated forms of microtubule-associated protein Tau

Question 19

Phosphorylation of Tau

Answer 19

Primary kinases responsible for phosphorylation are GSK-3a/B and CDK5
-Other kinases such as PKC, PKA and Erk2 are also involved

Question 20

Effect of phosphorylated Tau

Answer 20

-Hyperphosphorylation leads to the dissociation of Tau from the microtubule which is followed by microtubule destabilisation and oligomerisation which forms neurofibrillary tangles
-Accumulation of tangles leads to neuron apoptosis

Question 21

Mental health status testing

Answer 21

Doctors perform thinking (cognitive) and memory skills tests
-These scores are used to evaluate degree of cognitive impairment

Question 22

Neuropsychological tests

Answer 22

-Conducted by a specialist trained in brain conditions and mental health conditions (neuropsychologist)
-Evaluation can include extensive tests to evaluate memory and thinking (cognitive) skills

Question 23

Laboratory tests

Answer 23

-Measure accumulation of amyloid and tau proteins from cerebrospinal fluid
-ratio of these proteins can help determine alzeihmers presence
-Most cases, cerebrospinal fluid test is unnecessary and is only useful in atypical or rapidly progressive cases

Question 24

AD treatment

Answer 24

-No cure
-Best way to treat is through palliative care (reduce symptoms but not cure or change disease)
-Some medications can potentially slow down AD but not to a significant extent

Question 25

AD medication

Answer 25

Acetylcholine esterase inhibitor like Rivastigmine

Question 26

AD summary

Answer 26

Dysregulation of processing of Ab in phosphorylated Tau leads to formation of plaques and development of AD
-Enzymes such as a-secretase has a crucial role in pathogenesis of AD