neurodegenerative disorders

Question 1

What is the most common cause of dementia?

Answer 1

Alzheimer’s disease

Question 2

How are the early stages of AD described?

Answer 2

memory and insight loss, red. spontaneity, disorientation, apraxia, m. rigidity

Question 3

How are the late stages of AD described?

Answer 3

mutism, stupor, vegetative states, emaciation and death

Question 4

What are the gross findings of AD?

Answer 4

cerebral atrophy
dec in brain weight and volume
increase in ventricular volume

Question 5

What are the microscopic findings of AD?

Answer 5

senile plaques and A4/beta amyloid
neurofibrillary tangles
granulovacuolar degeneration
hirano bodies

Question 6

Senile plaques contain?

Answer 6

degenerating ‘neurites’

A4/beta amyloid peptide

Question 7

What is the molecular pathway for the generation of A4/beta amyloid?

Answer 7

Chrom 21 APP is cleaved by alpha/beta/gamma secretases. A4/beta accumulates and is neurotoxic

Question 8

Where can A4/beta be found?

Answer 8

in cores of plaques of AD
preamyloid diffuse plaques
artery walls of AD- familial amyloid angiopathy

Question 9

What genetic association is made for individuals with sporadic AD? Why?

Answer 9

apolipoprotein E isoforms (4>3>2)

ApoE4 increases amyloid deposition

Question 10

What causes the formation of neurofibrillary degeneration?

Answer 10

truncated microtubule associated protein-Tau

Question 11

What is the timeline and topographical distribution of pathology in AD?

Answer 11

limbic > subcortical basal forebrain and mam. bodies > association cortices

Question 12

Whast events cause cerebrovascular dementia?

Answer 12

cerebral infarcts
lacunar infarcts
watershed infarcts/laminar cortical necrosis
Binswangers disease

Question 13

What setting do we see Binswanger disease?

Answer 13

hypertensive cerebrovascular disease:

atherosclerosis and hyaline sclerosis

Question 14

How is Pick disease described?

Answer 14

rare degenerative dementing disorder with fronto-temporal degeneration

Question 15

What is the molecular pathogenesis of Pick disease?

Answer 15

abl Tau protein accumulating as intracytoplasmic Pick bodies, leading to neuronal loss and gliosis

Question 16

Progressive supranuclear palsy involves what brain systems?

Answer 16

nigrostriatal,
pallidum,
paramedian brainstem,
and cerebellar dentate nuclei

Question 17

What symptoms does Progressive Supranuclear palsy cause?

Answer 17

parkinsonism and vertical gaze paresis

Question 18

Microscopically, what is seen for PSP?

Answer 18

neurofibrillary tangles- a tauopathy

Question 19

What are the classic symptoms of idiopathic PD?

Answer 19

akinesia, rigidity, tremor, abl posture, gait and a flat affect

Question 20

What is the physiological cause of these symptoms?

Answer 20

loss of dopaminergic input to the caudate and putamen, causing substantia nigra degeneration (pigmented neuron loss)

Question 21

The lewy bodies of PD contain?

Answer 21

alpha synuclein

Question 22

What is the clinical course of ALS?

Answer 22

weakness and wasting of extremities, then bulbar, then respiratory failure. 3-5 years after dx.

Question 23

ALS causes degeneration of what parts of CNS?

Answer 23

upper and lower motorneurons:
corticospinal tract and
spinal anterior horn

Question 24

What does a biopsy of ALS look like?

Answer 24

denervated and atrophic

Question 25

What neurons are degenerated in HD?

Answer 25

medium spiny neurons of neostriatum

Question 26

What is the genetic cause of HD?

Answer 26

CAG repeats on HD gene of chromosome 4