Neuropathology of Parkinson's Disease

Question 1

Is PD more common in males or females?

Answer 1

Males

Question 2

What is the prevalence of PD in males and females?

Answer 2

19 per 100,000 men, 9.9 per 100,000 women

Question 3

Give 4 cardinal features of PD

Answer 3

Bradykinesia, postural instability, tremor, and (cogwheel) rigidity

Question 4

How much must dopamine levels be depleted by before symptoms appear?

Answer 4

70%

Question 5

What causes the impaired mobility in PD?

Answer 5

When dopaminergic neurons in the substantia nigra die, the reduction in dopamine release in the striatum causes cholinergic neurons there to overstimulate their targets, impairing mobility

Question 6

What is the difference between PD with dementia, and dementia with Lewy bodies?

Answer 6

In PD with dementia, the dementia onset is more than a year after the onset of PD. In dementia with Lewy bodies, the dementia is evident before or within a year of akinetic-rigid syndrome (PD)

Question 7

Where is the main site of Lewy bodies in PD?

Answer 7

Substantia nigra

Question 8

Name an alpha-synucleionpathy than causes parkinsonism other than PD

Answer 8

Multiple system atrophy (MSA)

Question 9

Name at least two tauopathies which cause parkinsonism

Answer 9

Progresisve supranuclear palsy (PSP), corticobasal degeneration (CBD), Guam Parkinson dementia complex

Question 10

Name a TDP-43 disorder which causes parkinsonism

Answer 10

Perry syndrone, frontotemporal lobar degeneration

Question 11

Name a toxic cause of non-degenerative parkinsonism

Answer 11

MPTP, manganese poisoning

Question 12

Which virus typically causes post-encephalitic parkinsonism?

Answer 12

Influenza

Question 13

Which class of drugs typically cause drug-induced parkinsonism?

Answer 13

Anti-psychotics

Question 14

In which area of the substantia nigra is neuronal loss typically the most pronounced in PD?

Answer 14

Ventrolateral

Question 15

Which pathways are most affected by PD?

Answer 15

Nigrostriatal

Question 16

Does PD typically affect mesocortical pathways?

Answer 16

No

Question 17

How do adult substantia nigra pars compacta neurons have a distinct physiological phenotype?

Answer 17

They have pacemaker-like properties leading to frequent intracellular calcium transients, in order to maintain a basal dopaminergic tone in target structures and permit movement

Question 18

Why are ventral tegmental area dopaminergic neurons less susceptible to PD?

Answer 18

Unlike substantia nigra pars compacta neurons, they have no calcium transients and lower calcium channel density. They also express high levels of the calcium ion buffering protein calbindin. This is believed to make them less suceptible

Question 19

Describe the appearance of the substantia nigra post-mortem in PD patients

Answer 19

Paler than normal due to loss of melanin (dopaminergic neurons are melanin pigmented)

Question 20

What causes alpha-synuclein to change conformation to an alpha-helix in normal physiology?

Answer 20

Exposure to negatively charged lipids

Question 21

Where is alpha-synuclein located in healthy individuals?

Answer 21

Pre-synaptically

Question 22

What are Lewy bodies?

Answer 22

Tightly packed inclusions of alpha-synuclein

Question 23

How are type B alpha-synuclein oligomers toxic to cells?

Answer 23

They intercalate themselves into the membrane and form a pore, resulting in toxicity

Question 24

Describe the neuritic body hypothesis of Lewy neurodegeneration

Answer 24

Lewy bodies form in the synaptic terminal, where alpha-synuclein is most concentrated, and then are retrogradely transported into the axon towards the cell body, where they cause the largest burden of pathology

Question 25

According to the Braak hypothesis, where does Lewy body pathology start in the brain?

Answer 25

Dorsal motor nucleus of vagus and the anterior olfactory nucleus

Question 26

Where are Lewy bodies found in Braak stage 3?

Answer 26

Central subnucleus of the amygdala, substantia nigra, nucleus basalis of Mynert

Question 27

Where are Lewy bodies found in Braak stage 4?

Answer 27

Transition zone between allocortex and neocortex, anterior cingulate

Question 28

Where are Lewy bodies found in Braak stage 5?

Answer 28

Insular and cingulate cortices

Question 29

Describe the difference in frontal-executive deficits between PD dementias and AD

Answer 29

In PD, frontal-executive deficits develop early and are prominent. In AD, these develop later and are less severe

Question 30

Describe the difference in memory deficits between PD dementias and AD

Answer 30

In PD, retrieval memory is impaired but encoding memory less affected. In AD, early memory complaints are common with both retrieval and encoding memory affected

Question 31

Describe the difference in visuospatial deficits between PD dementias and AD

Answer 31

In PD, impairments are often found. In AD, they are present but much less pronounced

Question 32

Describe the difference in behavioural deficits between PD dementias and AD

Answer 32

In PD, visual hallucinations are common. In AD, hallucinations are uncommon, with suspiciousness and disinhibition more common

Question 33

Where are Lewy bodies found in Braak stage 1?

Answer 33

Dorsal motor nucleus of vagus in the medulla

Question 34

Where are Lewy bodies found in Braak stage 2?

Answer 34

Locus coeruleus in the pons