Biochemistry Flashcards
What is BACE?
Beta amyloid cleaving enzyme/ B-secretase
Alzheimers disease is characterized by two important biochemical proteins; what are they?
Amyloid beta plaques
tau aggregates/ neurofibulary tangles
What are the greatest risk factors for developing alzheimers?
aging and genetics
Is alzheimers more than just mild cognitive impairment?
yes, it is a lethal disease of progressive neurodegeneration. Brain atrophy especially near the hippocampus
mild cognitive development means changes in language and judgement; not just memory loss.
Can you look at plaque accumulation in the living alzheimers patient?
yes, you can also see how glucose levels decrease in the brain.
What’s the amyloid beta plaque hypothesis for alzheimers disease? How is it different from the oligomer hypothesis?
plaques lead to inflammation formation of tau tangles and widespread neuronal death and dementia.
The oligomer hypothesis suggests that plaques maybe protective and are used in an effort to sequester oligomers which damage neurons.
What maybe the most promising type of therapy for alzheimers disease?
One which starts prior to plaque accumulation, initiated when biomarkers detect the disease early on.
What are amyloid beta and tau used for in the brain? How do things go wrong?
signaling molecules
these proteins at high concentrations can fold and amyloid can aggregate into beta sheets These beta strands are perpendicular to amyloid fiber axis
Where is the amyloid precursor protein located? What cleaves it and what are some alternative pathways? Which form of amyloid beta is found in the highest concentration in plaques?
Cell membrane
beta-secretase/BACE/beta amyloid cleaving enzyme
Amyloid beta 42
How would a alpha secretase activator affect alzheimers theoretically? alpha inhibitor? What about beta and gamma?
alpha-secretase inhibitor BAD activator GOOD
beta secretase inhibitor GOOD activator BAD
gamma secretase inhibitor GOOD activator BAD
What’s more common sporadic or familial alzheimers? Which has an earlier onset?
sporadic is more common
familial is earlier onset- genetic anticipation?
Which is NOT a genetic risk factor for alzheimers
a) presinilin 1
b) ApoE gene
c) APP
d) MIC gene
D
The rest are risk factors; and include presinilin 2 as well
What do the presiniins do? ApoE?
They are part of the gamma secretase cleavage of APP
ApoE interacts directly with Amyloid beta and plays a role in its clearance. The E4 variant is slower at amyloid beta clearance; leads to increased risk of alzheimers.
Gain of function mutations normally have what type of phenotype?
Dominant
How do polymorphisms in the ApoE gene affect alzheimers risk?
ApoE2 decreases risk
ApoE4 increases risk
ApoE binds to lipids and carries them as lipoproteins from clls that make lipids to cells that need them.
