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Flashcards in Pathogenesis of dementia Deck (27):

List three major neurodegenerative diseases associated with abnormal protein conformations?

Azheimer's disease

Creutzfeldt-Jakob disease

Parkinson's disease 


Describe the genetic risk factors for Alzheimer's disease?

Chromosome 21 (APP mutations)

Chromosome 19 (Apolipoprotein E)

Chromosome 14 (PS 1)

Chromosome 1 (PS 2)


Down's syndrome (trisomy 21)


Describe the environmental risk factors for developing Alzheimer's disease?

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Which has a larger impact on the development of AD: genetic or environmental risk factors?

Genetic factors 


Describe the four basic types of AD?

Amnestic (temporal)

Visuospatial (R>L)

Aphasic (L>R)



What are the two major pathologic lesions in the brain in AD?

Amyloid-beta plaques

Neurofibrillary tangles 


Describe how amyloid-beta plaques form in AD?

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How do neurofibrillary tangles form in AD?

Aggregation of tau, thought to be driven by amyloid beta peptide 

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Which part of the amyloid protein is thought to induce the pathogenesis of AD?

After short peptode released from TM domain, reforms as tetramer or dimer

These oligomers get stuck on or near synapses and interfere with normal processes of transmission, leading to degeneration 

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Describe one approach to taregtting the Ab oligomer in treating AD?


Metal-protein attenuating compound

Small proteins that can cross BBB and cause compete with metals for binding sites on Ab dimers > dimers fall apart and can be processed 


Describe the current approach to diagnosing AD?

1) Measuring Ab peptide in CSF

2) Radiolabelled ligand which binds amyloid filaments > PET scan

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Describe how Ab levels vary in Alzhemier's compared to health controls?

AD patients sit above arbitrary cutoff of 1.5

However, lots of healthy controls and patients with MCI also sit above this cutoff > are on their way to developing AD

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Describe the progression of Ab deposition over time?

Takes thirty years to move from completely normal to full blown AD

Takes 20 years to move from 1.5 cutoff to full blown AD

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Within which category of diseases does Creutzfeldt-Jakob disease belong?

Transmissible Spongiform Encephalopathies 


What is the natural host of CJD?



In which countries does CJD occur?

At what rate?

Sporadically all around the world 

1 in 1 million 

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What is kuru characterised by?

Tremors and shaking

Cerebellar degeneration 


Briefly describe how kuru was acquired?

Infectious disease

Women and children exposed when they dismembered dead bodies 


Describe the similarirties in causes between kuru and BSE?

Kuru: feeding humans to humans

BSE: feeding cattle to cattle 

Both due to cannabilism 


Describe the histological appearrance of brains affected by BSE?

Vacuoles developing within neuropil 

Fluid filled, membrane bound bound holes sitting in the cells of neurons 

Many astrocytes reacting to damage to nerve cells 

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Which molecule is responsible for the development of BSE?

How does it differ to normal?

PrPres (prion protein)

Has beta pleated sheet, which makes it insoluble and resistant to degradation 

Has ability to induce normal form (PrPc) to take on same shape 

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What is vCJD?

Variant CJD

New form of human BSE affecting young individuals after infected BSE carcasses entered human food supply

Presented in form similar to kuru - cerebellar predominance, neuropsychiatric phenomena


Why are people who lived in the UK (in specified period) prohibited from donating blood?

vCJD blood is infectious

Estimated incubation period is 6-15 years > peak exposure of BSE was in 1988-1993 > blood infectivity now at peak


Describe the brain area affected by PD?

Dopaminergic neurons in substantia nigra


Which molecule, other than DA, has been implicated in the development of PD? 


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Describe the molecular pathway which underlies PD?

a-synuclein comes into contact with Da > becomes redox active > combination induces a-synuclein to fold abnormally > becomes insoluble 

Lewy Body inclusions 

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