B2.022 Intro to Neurodegenerative Neuropathology

Question 1

where is atrophy especially prominent in a brain with AD?

Answer 1

temporal pole, medial temporal lobe (amygdala and hippocampus), frontal lobes, parietal lobes

Question 2

what happens to a cortex with AD?

Answer 2

reduced volume (thin)

Question 3

what happens to the ventricles in AD?

Answer 3

enlargement of lateral and 3rd (due to atrophy of amygdala and hippocampus)

Question 4

how does the brain weight change in AD?

Answer 4

reduced due to cerebral atrophy and loss of brain volume

Question 5

which part of the brain remains unaffected in AD?

Answer 5

cerebellum

Question 6

are B amyloid plaques intra or extracellular?

Answer 6

extracellular

Question 7

outline the Thal stages of B amyloidosis

Answer 7

1. cortex
2. amygdala, hippocampus
3. thalamus
4. brain stem
5. cerebellum

Question 8

how are the Thal stages used?

Answer 8

used in evaluation of people who die from neurodegenerative disease

Question 9

what is vascular B amyloid?

Answer 9

smooth muscle in blood vessels is replaced by B-amyloid

Question 10

what are some effects of vascular B amyloid?

Answer 10

can break and bleed causing possible hemorrhages even without hypertension

Question 11

what is the definition of amyloid?

Answer 11

pathologic proteinaceous substance, deposited between cells in various tissues and organs of the body in a wide variety of clinical settings

Question 12

describe the physical nature of amyloid?

Answer 12

made up largely of nonbranching fibrils of indefinite length, characteristic cross B pleated sheet conformation,

Question 13

what is the distinctive staining associated with B amyloid?

Answer 13

birefringence of Congo red stained amyloid, switch between yellow and salmon colors with different filters

Question 14

how do tau positive tangles differ from B amyloid plaques?

Answer 14

intracellular, different order of progression

Question 15

what are two other protein aggregates associated with AD?

Answer 15

alpha synuclein (also associated w Parkinsons)
TDP-43

Question 16

what makes tau proteins abnormal?

Answer 16

hyperphosphorylation

Question 17

what are some sources of misfolded proteins?

Answer 17

stress, cellular aging, mutations

oxidative stress: post translational modifications

Question 18

what are the cellular responses to misfolded proteins?

Answer 18

refolding, degrading, or sequestering the proteins

Question 19

what are mediators of protein degradation?

Answer 19

chaperone proteins, lysosomal pathways, ubiquitin-proteasome pathways

Question 20

what are major contributors to atrophy?

Answer 20

dendritic and neuronal losses

Question 21

what type of dementia is marked by focal frontal/temporal lobar atrophy?

Answer 21

frontal temporal dementias

Question 22

what is associated with vascular dementia?

Answer 22

signal changes in white matter

Question 23

what is an FGD-PET?

Answer 23

fluorodeoxyglucose PET scan, indicator of brain metabolism, hypometabolic regions (parietal, lateral, temporal, posterior cingulate) typical of AD

Question 24

discuss hypometabolism as a robust biomarker of neurodegeneration

Answer 24

hypometabolism can be observed to precede the appearance of cognitive symptoms and to predict the rate of progressive cognitive decline in individuals who are later found to have progressed to AD

Question 25

what new compound is used in imaging brain amyloid?

Answer 25

pittsburg compound B, based on thioflavin T

Question 26

can you have AB plaques and not show clinical signs of AD?

Answer 26

yes; plaque builds over a long period of time and often does not show clinical symptoms at the beginning