Huntington's Pathology

Question 1

What is the underlying pathogenesis feature of HD?

Answer 1

loss of neurons in the basal ganglia - specifically spiny striatal neurons

then loss of neurons from the cortex

Question 2

What motor dysfunction occurs in HD?

Answer 2

choreoathetosis (increased motor output)

Question 3

What gross abnormality will you see in an HD brain?

Answer 3

atrophy!

It’s small - you lose mass in the striatum and frontal lobe, leading to dilated lateral and 3rd ventricles

Question 4

What form of hydrocephalus occurs in HD?

Answer 4

hydrocephalus ex cavuo (due to neuron loss)

Question 5

What is the grading system for HD?

Answer 5

0 - no changes

1 - no atrophy, but microscopic changes

2 - microscopic changes and atrophy, but caudate still convex

3 - microscopic hcanges and atrophy - caudate flat

4 - microscopic changes and atrophy - cadate concave

Question 6

What else will you see on histology instead of death of spiny neurons?

Answer 6

fibrillary gliosis

hungintin protein aggreagate in neurons

Question 7

What do we use to stain the Huntingtin protein?

Answer 7

use the ubiquitin stain on the caudate

it will look brown under stain

Question 8

What is ubiquitin?

Answer 8

it’s a prtoein that tags misfoldd prtoeins and marks the for removal

so it tages the huntingtin protein, but it doesn’t get rmeoved by proteosomes like it shoulds, so it builds up

if you stain ubiquitin it will essentially stain the hungingtin.

Question 9

How else can you see huntginting aggregates under microscope?

Answer 9

electron microscopy - you’ll see the “basketlike’ structure that catches other proteins