Brainscape's Knowledge GenomeTM


Top Flashcards (Certified)
All Flashcards

Cellular Pathology > HistoPath of Proteinopathies > Flashcards

HistoPath of Proteinopathies Flashcards

1
Q

Define Proteinopathies

A
  • a disease which results from conformational changes in proteins, leading to altered functions
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
2
Q

Give some examples of Common Protienopathies

A
  • Alzheimer’s
  • Parkinson’s
  • Frontotemporal Lobar Degradation neuropathology
  • Creutzfeldt-Jakob disease
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
3
Q

What is dementia a syndrome of ?

A
  • intellectual deterioration
  • personality deterioration
  • confusion
  • impulse control
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
4
Q

What does dementia involve?

A
  • progressive loss of higher mental function & memory
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
5
Q

What are the 2 types of dementia ?

A
  • temporary
  • chronic
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
6
Q

Describe temporary dementia

A
  • medication side effect
  • symptoms can improve/disappear when treated
  • treatable
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
7
Q

Describe Chronic Dementia

A
  • occurs to permanent changes in the brain
  • progressive
  • lasts remaining life time
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
8
Q

What can cause dementia?

A
  • Alzheimer’s
  • Huntington’s
  • Stroke
  • Tumour
  • Head injury
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
9
Q

What’s the prevalence of dementia in 80-89 yr olds?

A

24.2%

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
10
Q

What causes Vascular Dementia ?

A

Transient Ischemic attacks

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
11
Q

What are some symptoms of Vascular Dementia ?

A
  • more rapid decline than AD
  • decline occurs in spurts
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
12
Q

What causes Frontal Lobe Dementia ?

A
  • damage to frontal lobes
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
13
Q

What are symptoms of frontal lobe dementia ?

A
  • personality changes = apathy, lack of inhibition, obsessiveness & loss of judgement
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
14
Q

What causes Parkinson’s disease?

A
  • lack of dopamine in basal ganglia
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
15
Q

What are some symptoms of Parkinson’s disease?

A
  • Tremors
  • shuffling gait
  • postural instability
  • speech problems
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
16
Q

What causes Lewy Body Dementia ?

A
  • accumulation of Lewy Bodies
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
17
Q

What are some symptoms of Lewy Body Dementia ?

A
  • confusion
  • hallucinations
  • motor deficits
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
18
Q

What causes Huntington’s Disease?

A

Htt mutations (Chr 4)

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
19
Q

What are some symptoms of Huntington’s Disease?

A
  • Choreiform movements
  • loss of detailed memories
  • speech impariment
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
20
Q

Describe what can cause Alzheimer’s Disease (AD)

A
  • Gene mutation in genes like APP, PSEN1 & PSEN2
  • Leads to increased production of amyloid beta peptides which accumulate as plaques in the brain
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
21
Q

Define Alzheimer’s Disease

A

Progressive disorder characterised by impairment of higher intellectual functions with alterations in mood & behaviour (thus causes dementia)

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
22
Q

What parts of the brain does Alzheimer’s predominantly affect?

A
  • Hippocampus
  • Limbic system
  • frontal cortex
  • also targets cholinergic neurons
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
23
Q

What are some symptoms of Alzheimer’s ?

A
  • memory loss that disrupts daily life
  • confusion in time & place
  • poor judgement
  • changes in mood & personality
  • increases anxiety, agitation & sleep disturbance
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
24
Q

What are the 2 hallmarks of Alzheimer’s ?

A
  1. Amyloid Plaques
  2. Neurofibrillary Tangles
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
25
Describe Amyloid Plaques
- clumps of protein fragments - between neurons - Amyloid Beta Proteins
26
Describe Neurofibrillary Tangle
- inside of neurons - made of Tau protein - Tau maintians microtubules within Axons - tangles form when tau changes chemically & can no longer support microtubules - leads to collapse of transport system within neuron
27
Describe the Pathogenesis of Alzheimer's Disease
- Unknown - involves build-up of Beta Amyloid Protein in the brain - Brain normally has a protein called APP - Alzheimers pateints are unable to remove this protein - results in accumulation of Beta Amyloid Protein around neurons - some build up is normal but way more occurs in Alzheimer's
28
What does an accumulation of Beta Amyloid Protein alter?
- Neurotransmission is affected, nerves struggle to communicate - large amount = neuronal cell death & neuroinflammation - small amount = toxicity at synapses - BAP also results in neurofibrillary tangles that contain tau protein
29
Under normal conditions, how can Amyloid precursor protein (APP) be processed ?
1. Non-amyloidogenic 2. Amyloidogenic
30
Describe the Non-amyloidogenic pathway
- involves cleavage of APP by a secretase to generate 2 fragments = C83 & sAPPa -cleavage prohibits A beta peptide production
31
What can the C83 membrane fragment be cleaved into?
- cleaved by y-secretase - produces a short fragment = P3 peptide & an APP intracellular domain (AICD)
32
Describe the Amyloidgenic Pathway
- leads to neurotoxic A beta generation -B-secretase meditates the 1st proteolysis step - large N-terminal ectodomain is released - 99-amino acid C terminal fragment remains in membrane - newly exposed C99 N-terminus corresponds to the 1st amino acid of A beta - successive cleavage releases the A beta peptide
33
How long are most A beta peptides?
- typically 40 residues in length - small percentage contain 42 residues
34
Why are the 42 residude long A beta peptides more neurotoxic ?
- 2 extra amino acids provide a greater tendency to misfold & subsequently aggregate
35
What have elevated plasma levels of A beta 1-42 been correlated with ?
Alzheimer's Disease
36
How can AD be definitively diagnosed?
- finding plaques & tangles in the brain
37
What is a barrier to understanding the role of Amyloid Beta in AD?
- Lack of correlation between A beta in the brain & cognitive ability of patients - some patients with A beta deposits show no symptoms of AD at all
38
What are some treatments for AD?
- Cholinesterase Inhibitors - Memantine - Anti-Amyloid Therapies - Lifestyle Interventions
39
Describe the function of Cholinesterase Inhibitors
= medications like donepezil & galantamine help improve cognitive function
40
Describe the function of Memantine
= it's an NMDA receptor antagonist that may slow down cognitive decline
41
Describe the function of Anti-Amyloid Therapies
- ongoing research focuses on targeting A beta plaques using monoclonal antibodies like aducanumab
42
What are some examples of modifiable risk factors for AD?
- cardiovascular disease risk = health of brain closely linked to heart & blood vessel health - smoking - midlife obesity - diabetes - hypertension - high cholesterol - Education
43
Describe why Education is a modifiable risk factor for AD
- people with fewer years of education are at higher risk of development of AD compared to those with more years of formal education - Higher educated individuals are more likely to have occupations that are more mentally stimulating
44
Describe the Cognitive reserve hypothesis
- having more education enables individuals to best compensate for brain changes - connectivity between neurons is better - use alternate routes of neuronal-to-neurone communication
45
How can Amyloid Beta plaques be visualised?
- PET Scans with radio-labelled molecules that bind to amyloid beta - brighter signals correlate to higher amyloid beta accumulation
46
How can Aducanumab help clear amyloid beta plaques?
= Aducanumab = human antibody to A beta fragments - immunotherapy - Aducanumab binds to Amyloid beta plaques & immune cells carry plaques away to be dissolved
47
Describe Tau
- tau = microtubule-associated protein - plays an important role in assembly & stabilisation of microtubules & regulates axonal transport
48
Describe Abnormal Tau
- Hyperphosphorylated - assembled into insoluble filaments which then accumulates in neurons and/or glial cells
49
Where is Tau found ?
- inside of neuronal cells - where it can form intracellular tangles
50
Define Tauopathies
- a class of neurodegenerative disorders characterised by neuronal and/or glial inclusions composed of microtubule-binding protein, tau
51
How are Tauopathies classified?
- by the predominance of tau isoforms found in cystoplasmic inclusions
52
What are a 3R-Tauopathies ?
- inclusions predominately composed of tau with 3 MTBDs
53
Describe 4R-Tauopathies
- inclusions are predominantly 4 MTBDs or an equal ratio of 3R:4R tau
54
Describe Microtubule Detachment with abnormal tau
- In Alzheimer's & related Tauopathies tau detaches from microtubules - microtubules weaken & collapse - abnormal tau clumps together, forming neurofibrillary tangles - these impair neuronal communication & contribute to cell damage
55
How many known pathogenic mutations are known in the MAPT tau gene ?
- Over 40 which result in tauopathies
56
How are MAPT pathogenic mutations thought to cause disease ?
1. inhibiting the normal microtubule-binding function of tau 2. promoting tau protein aggregation 3. affecting the splicing of exon 10 to result in imbalances between 3R & 4R tau isoforms
57
How many Tauopathy histological subtypes are there ?
-8 - A, B,C,D,E,F,G,H
58
Describe the Epidemiology of Parkinson's
- juvenile onset is rare - 125,000 affected in the UK today - 1% >60 yr old affected - 3% >70 yr old affected
59
Describe the Characteristics of Parkinson's disease
- resting tremor - muscular rigidity - postural instability - gait abnormalities - preferential loss of dopaminergic neurones throughout the brain, especially in Substantia Nigra = Brain area controlling movement
60
When do Parkinson's symptoms become apparent?
- When 80% of neurones in the Substantia Nigra have been lost
61
Describe the Braak Hypothesis 2003
- Neuroinvasion by unknown pathogen - Some evidence that gut neurones are affected before the CNS - Possible that a pathogen could start in the gut & show neurotropism - no evidence to support this theory
62
Describe Familial PD
- Much rarer than idiopathic PD - many identified mutations occur in just 1 or a few families
63
What are some possible treatments for Parkinson's disease?
- Levodopa/Carbidopa - Dopamine Agonists - Deep Brain Stimulation - Gene Therapies
64
Describe characteristic of Prion-like behaviour
- protein-based templated misfolding - polymorphic 'strains' propogation along neuronal systems - remarkable stability of pathologic aggregates
65
Describe the Prion Protein
- PRNP = Single-copy gene with 3 exons - Exon 1 coding for PrP - PrP C shows a developmentally regulated expression pattern in skeletal muscle, kidney, heart, CNS - In the CNS high PrP expression is found in the synaptic membranes of neurons, and the protein is also expressed in astrocytes
66
Describe the Prion Hypothesis
- Proposes that disease progression & infectivity propagate by recruitment & "autocatalytic" conformational conversions of endogenous PrP C into disease-associated PrP Sc
67
Describe the Histopathology of Creutzfeldt-Jakob disease
- neuronal loss - astrocytic gliosis - microgliosis - synaptic loss - Spongiform change
68
Describe Neuronal Loss
- Pattern of loss is variable - loss is usually exaggerated in cortical layers & in focal regions of the caudate nucleus & thalamus
69
Describe Astrocytic Gliosis
- Reactive Asstrocytosis in CJD seems more intense that would predicted by the degree of nerve cell loss
70
Describe Microgliosis
- Microglial hypertrophy & hyperplasia show widespread distribution in prion disease
71
Describe Synaptic Loss
- Ultrastructural studies have shown that axons & dendrties are damaged early during the disease course
72
Describe Spongiform Changes
- characterised by small, round/oval vacuolated empty spaces in the neuropil surrounding neurons - these spaces give the brain tissue a sponge-like appearance
73
What does Gliosis refer to?
Refers to the proliferation of glial cells in response to injury

Cellular Pathology (22 decks)

Brainscape helps you reach your goals faster, through stronger study habits.
© 2025 Bold Learning Solutions. Terms and Conditions