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Flashcards in Pathogenesis of Dementia Deck (19):
1

What is the abnormal protein conformation in AD?

APP and Aβ amyloid

2

What is the abnormal protein conformation in Creutzfeldt-Jakob disease?

Prion protein

3

What is the abnormal protein conformation in PD?

Alpha-synuclein

4

List 4 sites for genetic mutations conferring susceptibility to AD

Chr 21 (APP)
Chr 19 (APOE)
Chr 14 (Presenilin-1)
Chr 1 (PS-2)

5

Which genetic mutation confers susceptibility to the sporadic form of AD?

Chr 19 (APOE)

6

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

7

What are the 4 basic types of AD and their associated topographical basis?

Amnestic (temporal)
Visuospatial (more commonly right-sided)
Aphasic (more commonly left-sided)
Frontal

8

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

9

How many mg of Aβ amyloid plaque must accumulate in the brain to cause AD?

10

10

What enzymes cleave APP to form amyloid?

Secretases

11

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

12

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

13

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?

10-12 years
~20 years

14

Give 3 examples of transmissible spongiform encephalopathies

Scrapie
Bovine spongiform encephalopathy (BSE; mad cow disease)
Kuru
Creutzfeldt-Jakob disease

15

What is the mean age of onset in CJD? How long does it take for death to occur?

~55 years
Death within 6 months

16

What is the primary deficit in kuru?

Progressive cerebellar degeneration

17

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)

18

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)

19

What is the pathological process in PD?

Aggregates of DA, iron and alpha-synuclein causing damage to alpha-synuclein and subsequent oligomerisation; this causes disruption of vesicles and decreased DA transmission