Flashcards in Pathogenesis of Dementia Deck (19):
What is the abnormal protein conformation in AD?
APP and Aβ amyloid
What is the abnormal protein conformation in Creutzfeldt-Jakob disease?
What is the abnormal protein conformation in PD?
List 4 sites for genetic mutations conferring susceptibility to AD
Chr 21 (APP)
Chr 19 (APOE)
Chr 14 (Presenilin-1)
Chr 1 (PS-2)
Which genetic mutation confers susceptibility to the sporadic form of AD?
Chr 19 (APOE)
List 5 risk factors and 2 possible protective factors for AD
Risk: low education, head trauma, smoking, vascular disease, diabetes
Protective: diet high in antioxidants, essential fatty acids
What are the 4 basic types of AD and their associated topographical basis?
Visuospatial (more commonly right-sided)
Aphasic (more commonly left-sided)
What forms the neurofibrillary tangles in AD? What drives the formation of these tangles?
Accumulations of tau (a microtubule-associated protein)
Their formation is driven by abnormal Aβ amyloid plaques
How many mg of Aβ amyloid plaque must accumulate in the brain to cause AD?
What enzymes cleave APP to form amyloid?
What is the best target for a disease-modifying drug in AD? Give an example of a prospective drug acting on this target
The Aβ oligomer (juts out into synapses, causing synaptic toxicity)
Metal-protein attenuating compound currently currently being trialled to target this
What imaging process is being used to diagnose AD even in its pre-clinical stages?
PET scans using a radio-labelled ligand (PiB) to examine for presence of Aβ amyloid plaques
What is the average time period from normality to threshold for AD? What is the average time period from threshold to mean level of Aβ deposition in an average AD patient?
Give 3 examples of transmissible spongiform encephalopathies
Bovine spongiform encephalopathy (BSE; mad cow disease)
What is the mean age of onset in CJD? How long does it take for death to occur?
Death within 6 months
What is the primary deficit in kuru?
Progressive cerebellar degeneration
What is the pathological process in scrapie and vCJD?
Conversion of PrPc (normal) to PrPres (abnormal; insoluble and resistant to degradation)
PrPres can also induce the normal form to take on the abnormal shape (an autocatalytic process)
What are the 2 most relevant genetic mutations affecting PrP?
Triplet repeat (if it becomes expanded, this can produce the more rare autosomal dominant form of disease)
SNP (methionine variant induces susceptibility to disease and is absent in most populations with previous epidemics)