Parkinson's Disease: Neuropathology Flashcards Preview

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Flashcards in Parkinson's Disease: Neuropathology Deck (26)
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1

Define Parkinson's disease

Progressive neurological disorder defined by bradykinesia, tremor, rigidity and postural instability (at least two)

[commonly associated features: autonomic disfunction, cognitive disturbance, depression, dysphagia]

2

Define parkinsonism

Clinical syndrome with some/all of the following features:

- bradykinesia
- tremor
- rigidity
- postural instability
- autonomic dysfunction/cognitive disturbance/depression/dysphagia

3

Define parkinsonian disorders

Disorders in which Parkinsonism is a prominent feature: akinetic-rigid disorders

4

What must occur before clinical symptoms of Parkinson's appear?

Loss of 80-85% of dopaminergic neurons and deplete dopamine levels by 70%

5

Describe how Parkinson's can be modelled in animals?

MPTP: a prodrug to the neurotoxin MPP+

Can be accidentally produced during manufacturing of the opioid drug desmethylprodine (MPPP)

Intoxication causes parkinsonism associated w/ degeneration of dopaminergic neurons

6

PD:

Site of LBs and clinical correlate?

LBs in substantia nigra

Akinetic-rigid syndrome

7

Parkinson's w/ dementia (PDD):

Site of LBs and clinical correlate?

LBs in substantia nigra and cerebral cortex

Dementia ≥1 y after dx
of PD

8

Dementia w/ Lewy Bodies:

Site of LBs and clinical correlate?

LBs in substantia nigra and cerebral cortex

Dementia <1 y after
akinetic-rigid syndrome

9

How can we classify Parkinson's?

Degenerative:
- a-synuclein (PD, MSA)
- tau (prog supra palsy, CTE)
- TDP-43 (fronto-temporal lobar degen)
- nonspecific (genetic)

Non-degenerative:
- vascular
- toxic (MPTP, manganese poisoning)
- drug induced (antipsychotics
- infectious (flu)

10

Pathological features of Parkinson's disease

Neurodegeneration accompanied w/ neuronal inclusions composed of alpha-synuclein (Lewy Bodies)

11

Pathological correlate of the symptoms of Parkinson's

Neuronal loss in the substantia nigra (ventrolateral) and dopaminergic denervation of the striatum

12

Describe physiological phenotype of DA neurons in the substantia nigra (SN)

Pacemaker-like properties lead to frequent intracellular calcium transients

Pacemaking maintains basal DA tone in target structures- without it there is no movement

13

Describe physiological phenotype of DA neurons in the ventral tegmental area (VTA)`

Slow pacemakers

No calcium transients

Less Ca2+ channel density

High levels of calbindin (Ca2+ buffer)

14

What is alpha-synuclein?

Abundant in brain

Unknown physiological function (maybe regulates synaptic plasticity and NT release?)

15

Diagnostic Gold Standard for PD?

alpha-synuclein immunostaining

16

Describe the oligomers of alpha-synuclein

A: normal
B: implants into membrane, forming pore -> cellular dysfunction

17

Neuritic dystrophy hypothesis of neurodegradation

a-synuclein is transported from axon->synapse

Misfolding of a-helix to b-sheet -> aggregation -> axonal transport disrupted -> a-syn accumulates

18

Braak PD staging

1. dorsal motor nucleus of vagus nerve
2. locus coeruleus
3. substantia nigra
4. basal forebrain
5. cortex

19

Braak's perception of PD progression

Begins in dorsal motor nucleus of vagus nerve and anterior olfactory nucleus

Proceeds rostrally towards neocortex

20

Role of gut in PD?

PD hypothesised to start in gut peripheral ganglia- Gut biopsies to test for PD, constipation may be presenting symptom

21

Role of olfactory bulb in PD?

exposure to organophosphpates?

agricultural workers have higher PD incidence

Anosmia found 10-20 yrs prior to motor symptoms PD

22

Dual hit hypothesis for PD?

Genetic susceptibility w/ environmental trigger -> PD

23

MSA pathology?

glial inclusions of alpha-synuclein

24

PDD/DLB vs AD clinical features?

PD: frontal-executive + visuospatial + memory retrieval

AD: memory presentation (encoding)

25

Prion hypothesis of alpha-synuclein?

Prion like spread of pathology may underlie all proteinopathies- alpha-synuclein may spread in a prion-like fashion

26

ALL PATHOLOGICAL EXAMPLES

CHECK OLDER YEARS NOTES FOR THESE AS STUDIES HAVE BEEN OMITTED FROM ALL MY FLASHCARDS LOL