Dementia Flashcards
What is the most common type of dementia?
Alzheimers Disease
Vascular Dementia
Mixed AD + VaD
Dementia with Lewy Body
What is the most common type of dementia?
Alzheimers Disease
Vascular Dementia
Mixed AD + VaD
Dementia with Lewy Body
Name 4 non-modifiable risk factors for dementia [4]
Name 4 modifiable risk factors for dementia [4]
Non-modifiable risk factors
* Age (greatest risk factor)
* Genetic predisposition
* Family history
* Downs syndrome
Modifiable risk factors
* Vascular Risk factors (high cholesterol, hypertension, diabetes)
* Cognitive inactivity (low education attainment)
* Environment (head injury)
* Depression
Pathogenesis of Alzeimers DIsease (AD)
State the name of this protein [1]
Where is it found within the cell? [1]
Amyloid plaque - found in cytosol
Early disease progession
Pathogenesis of Alzeimers DIsease (AD)
State the name of this protein [1]
Where is it found within the cell? [1]
Is it associated with early or late disease progression? [1]
Tau intraneuronal
Later disease progression
Pathogenesis of Alzeimers DIsease (AD)
Name the genes [3] and proteins [3] that are critical for early onset AD [3]
Genes for early onset AD (not common). caused by the following genes
* Amyloid precursor protein (APP)
* Presenellin 1 (PSEN1)
* Presenellin (PSEN2)
Pathogenesis of Alzeimers DIsease (AD)
What is the final product of amyloid precursor protein being cleaved? [1]
Aβ peptides (this is a normal metablic event)
Which gene is associated with late onset AD? [1]
Late onset (60+ years of age)
* Apolipoprotein E (Ch.19)
Presenilin 1 & 2 are responsible for making which secretase? [1]
Presenilin 1 & 2 proteins is one part (subunit) of a complex called gamma- (γ-) secretase.
Describe the difference in APP processing between the amyloidogenic and non-amyloidogenic pathway
APP protein has 3 cleaving sites. Depending on combination of secretases have will cause different payhways
Non-amyloidogenic pathway:
* alpha-secretases and gamma-secretases
Amyloidogenic pathway:
* Beta-secretases and gamma-secretases
* Generates: AB peptide with two isoforms:AB 40 and AB 42.
Label A-D
A: gamma secretase
B: alpha secretase
C: Beta secretase
D: gamma secretase
Name the two isoforms of AB protein that form insoluble plaques
AB 40 and AB 42
Describe the inflammatory response caused by familial forms of AD pathogenesis (from early AD genes) [2]
Describe the effect of amyloid plaques within neurons (caused by familial forms of AD pathogenesis) [2]
Inflammatory response:
* Microglial activation - inability to clear AP causes chronic inflammation of microglia
* Astrocytosis (increase in amount) and acute phase protein release
Progressive neuritic injury within amyloid plaques
* Disruption of neuronal metabolism and ionic homeostasis:
* Oxidative Stress
Which molecule is APOE involved in the metabolism of? [1]
What are the three isoforms of APOE? [3]
Which is the greatest risk for AD and why? [2]
Involved in cholesterol metabolism
APOE2; APOE3 & APOE4
APOE4 has greatest risk factor and decreases clearance of extracellular Aβ.
Which posttranslational modification does the microtubule-binding protein, tau undergo which contributes to Alzheimer’s pathology? [1]
Which amino acids can undergo this specific post translational modification? [3]
Hyperphosphorylation.
Tyrosine, serine and threonine.
Which change in AD pathophysiology relates to cognitive decline? [1]
Hyperphosphorylated tau tangles correlate to cognitive decline (Amyloid plaques does not)
