dementia neuropathology

Question 1

name four dementia disorders

Answer 1

1) Alzheimers disease
2) dementia with lewy bodies
3) frontotemporal dementia
4) vascular dementia

Question 2

which type of dementia is NOT a neurodegenerative disease?

Answer 2

vascular dementia

Question 3

which two things can be seen microscopically?

Answer 3

1) intraneuronal inclusion bodies

2) extra neuronal changes eg plaques

Question 4

which three things can be seen macroscopically in the brain of a patient with dementia?

Answer 4

1) region specific atrophy
2) generalised brain atrophy
3) enlarged ventricles

Question 5

which macroscopic feature may indicate what type of dementia a person has?

what is seen in i) Alz ii) FTD

Answer 5

region specific atrophy

i) Alz see shrinking of temporal lobe
ii) FTD see frontal shrinking which then moves anterior and temporal

Question 6

which three proteins misfold and abnormally aggregate in dementia?

Answer 6

amyloid, tau and synuclein

Question 7

Tau - true or false

i) it is a normal protein we have in our brains
ii) it has low solubility and is mostly found outside the brain
iii) there are 5 isoforms
iv) length varies between 352 and 411 amino acids

Answer 7

i) true
ii) false - it has low solubility and is predominantly found in the brain (in axons)
iii) false - there are 6 isoforms
iv) true

Question 8

what is the function of tau?

Answer 8

to modulate the stability of axonal microtubules and interneuronal transport

Question 9

which form of tau causes disease and what causes this?

Answer 9

the hyperphosporylated form caused by activation of kinases

Question 10

what does the hyperphosphorylated form of tau lead to and what does this cause?

Answer 10

HF tau leads to paired helical filaments which accumulate into neurofibrillary tangles which then cause NGD

Question 11

what allows the assembly of paired helical filaments from tau?

Answer 11

hyperphosphorylation of tau

Question 12

which two forms of dementia are tau abnormalities seen in?

Answer 12

alzheimers and FTD

Question 13

which type of tau has

i) damage inside neurons
ii) twisted helical filaments

Answer 13

neurofibrillary tangles

Question 14

which stain allows visualisation of NF tangles?

Answer 14

H&E

Question 15

which lobe are NF tangles most commonly found in?
what function does this lobe have?
what deficits does this therefore cause?

Answer 15

NF tangles are most commonly found in the temporal lobe

structure in temporal lobe are involved in memory and cognition
therefore leads to memory and cognition deficits

Question 16

apart from the temporal lobe - which brain areas do neurofibrillary tangles also cause problems in? (2)

Answer 16

hippocampus and amygdala

Question 17

when may amyloid begin to aggregate in relation to Alzheimers disease? (2)

Answer 17

before alz develops and before tau abnormalities are detected

Question 18

does amyloid cause intra or extraneuronal pathology?

Answer 18

extra neuronal

Question 19

what is the function of amyloid precursor protein in a physiological state?

Answer 19

it is a transmembrane glycoprotein on the surface of cells which is normally broken down and eliminated from the brain

Question 20

which two enzymes split APP?

Answer 20

beta and gamma secretases

Question 21

which isoform of beta amyloid is problematic and why?

Answer 21

Ab42 - 42 aa fragment

- is a problem because its very sticky and develops into amyloid plaques

Question 22

how does Ab42 cause damage and brain cell death? (3)

Answer 22

accumulates into amyloid plaques
produces a cytotoxic environment
recruits microglia and inflammatory agents to the site

Question 23

which proteins abnormally aggregate in Alzheimers? (2)

Answer 23

amyloid and tau

Question 24

what is the primary protein associated with FTD?

Answer 24

tau

Question 25

what type of dementia do you see intraneuronal pathology with ballooned neurons

Answer 25

fronto temporal dementia

Question 26

what are pick bodies? what dementia pathology are they found in?

Answer 26

pick bodies are rounded microscopic structures found within neurons and are aggregates of tau
found in FTD

Question 27

are plaques and tangles found in FTD?

Answer 27

no - just tau tangles

Question 28

which areas would be expected to be atrophied in FTD?

Answer 28

frontal and anterior temporal lobes

Question 29

what type of synuclein aggregates?

Answer 29

alpha

Question 30

what type of cells is synuclein found in (2) and what is its function? (3)

Answer 30

• found in neurons and glial cells

- functions in lipid vesicle binding, inhibition of kinases and DA uptake

Question 31

what type of protein has alpha synuclein been described as?

Answer 31

a chaperone

Question 32

which four areas is synuclein predominantly expressed in?

Answer 32

• neocortex
• hippocampus
• substantia nigra
• cerebellum

Question 33

dysregulation of which protein causes PD? why?

Answer 33

dysregulation of synuclein causes PD as its involved in DA uptake in the striatum

Question 34

which protein aggregates to form intracytoplasmic inclusions in neurons called Lewy bodies?

Answer 34

synuclein

Question 35

true or false about synuclein

i) intraneuronal aggregates
ii) seen only in PD
iii) fibrillary aggregates of beta synuclein protein

Answer 35

i) true
ii) false - seen in PD and dementia with lewy bodies
iii) false - fibrillary aggregates of alpha synuclein protein

Question 36

what three things are Lewy bodies made from?

Answer 36

1) alpha synuclein
2) ubiquitin
3) enzymes

Question 37

what type of aggregate can be described as spherical intranuclear cytoplasmic eosinophilic inclusions that are abnormally truncated and phosphorylated?

Answer 37

Lewy bodies

Question 38

what two types of brain damage may cause vascular dementia? give an example of both

Answer 38

1) ischaemic due to stroke/TIA

2) haemmorhagic due to bleeding of brain tissue

Question 39

what are the three most common mechanisms causing vascular dementia and what causes each?

Answer 39

1) single strategically placed infarct (caused by sudden stroke)
2) multiple cortical infarcts (from a TIA)
3) sub cortical small vessel disease (no event but low grade chronic build up)

Question 40

what may be the result of a single strategically placed infarct in vascular dementia?

Answer 40

sudden memory or cognition problems

Question 41

why might U&E be an important investigation when looking for dementia?

Answer 41

can detect hypernatremia (high sodium) which may cause confusion

Question 42

which type of scan is best to see cerebrovascular pathology?

Answer 42

MRI

Question 43

which type of scan can show difference between Alzheimers and DWLB? how does it do this?

Answer 43

SPECT scan

- achieves this by assessing the state of cells in the substantia migraine

Question 44

which scan can allow early indication of regional brain atrophy by injecting a tracer? what does the tracer target?

Answer 44

PET scan

- the tracer targets amyloid

Question 45

what are the four symptomatic treatments for Alzheimers? by which mechanism do these work?

Answer 45

donepezil, rivastigmine, galantamine and memantine

- work by inhibiting Ach esterase therefore increase amount of Ach in the synaptic cleft

Question 46

which type of dementia may SSRIs be given in to help with behaviour?

Answer 46

FTD