Genetics of neurodegenerative disease

Question 1

neurodegeneration

Answer 1

progressive loss of synapses and neurones in specific neuronal populations

Question 2

specific neuronal population lost in alzheimers disease

Answer 2

cholinergic neurones in basal forebrain (acetylcholine)

Question 3

specific neural population lost in parkinsons disease

Answer 3

dopaminergic neurones in the substantia nigra

Question 4

specific neural population lost in huntingtons disease

Answer 4

medium spiny GABAergic neurones in the striatum

Question 5

what is the leading cause of dementia

Answer 5

alzheimers disease

Question 6

3 pathological features of AD

Answer 6

1. plaques composed of amyloid beta peptide
2. neurofibrillary tangles composed of tau
3. inflammation composed of reactive glia

Question 7

plaques in AD

Answer 7

aggregates of sticky peptides that deposit in the brain
amyloid beta peptide produced from metabolism of a larger precursor
defining hallmark

Question 8

tau in AD

Answer 8

tangles of a microtubule stabilising protein that appear within neurones
defining hallmark

Question 9

reactive glia in AD

Answer 9

microglia in the brain are resident immune cells. they are recruited to and cluster around the amyloid beta peptide plaques

Question 10

main cause of AD

Answer 10

sporadic
biggest risk factor being age
GWAS identified some variants and risk loci

Question 11

once copy of which allele increases risk of AD?

Answer 11

ApoE4

Question 12

what can cause early onset of AD but is a far less common cause

Answer 12

familial AD>inheritance
autosomal dominant mutations

Question 13

autosomal dominant mutations causing AD

Answer 13

in amyloid precursor protein>gene on chromosome 21
presenilin 1 and 2

Question 14

downs syndrome and AD

Answer 14

gene dosage effects
amyloid precursor protein gene on chromosome 21

Question 15

PS1 and PS2

Answer 15

presenilin
enzymatic complexes involved in metabolism of amyloid precursor protein

Question 16

mutations in tau (MAPT)

Answer 16

do not give rise to inherited AD

Question 17

parkinsons disease majority cause

Answer 17

sporadic

Question 18

motor symptoms in PD

Answer 18

loss of dopamine innervation in basal ganglia

Question 19

PD pathology

Answer 19

lewy bodies composed of intracellular aggregates of alpha synuclein>a sticky protein in the brain
involved in secretion of dopamine

Question 20

SNCA gene PD

Answer 20

chromosome 4
autosomal dominant duplication mutations
alpha synuclein involved with synaptic vesicles
gene dosage effects

Question 21

LRRK2 PD

Answer 21

chromosome 12
kinase function
autosomal dominant mutations associated with enhanced risk

Question 22

parkin and UCHL1 genes in PD

Answer 22

involved in same process
addition of ubiquitin is signal for degradation of protein>failure to do so leads to protein aggregation in cells

Question 23

GWAS in PD

Answer 23

risk loci associated with inability to clear misfolded protein