Different Forms of Beta Amyloid: Causes of Alzheimer’s Disease
Interact with different forms of the Beta Amyloid protein and learn why one form may cause Alzheimer’s disease while the other does not. At The Emergent Universe, an online interactive science museum about emergence.
Celebrity Boxing: Beta Amyloid 42 vs. Beta Amyloid 40
Discover why Beta Amyloid 42 is more toxic than Beta Amyloid 40
How are Beta Amyloid 42 and Beta Amyloid 40 different?
- -Proteins are chains of molecular units called “amino acids.”
- -Some of these amino acid units are attracted to water, others are repelled by water, while others don’t care.
- -Beta Amyloid 40 has 4 sections: [diagram showing water-attracting, water-repelling, and water-ambivalent segments of Aβ40]
- -Beta Amyloid 42 is exactly the same except for 2 additional water-repelling residues on the very end: [diagram showing water-attracting, water-repelling, and water-ambivalent segments of Aβ42]
How does this make Beta Amyloid 42 more toxic?
Try to create clusters from different types of Beta Amyloid to find out.
Choose the last two units for Beta Amyloid (beta amyloid):
- (Aβ40) amyloid beta 40
- (Mutation 1)
- (Mutation 2)
- (Aβ42) amyloid beta 42
What size cluster can you make?
Beta Amyloid 40 doesn’t easily form clusters of more than 4 molecules. Try a different Aβ?
Adding 2 water-ambivalent units to Beta Amyloid 40 doesn’t change its clustering behavior at all. Try a different Aβ?
Changing the 42nd unit to water-repelling is enough to cause clusters of 5 or 6 molecules to be more stable. Will these clusters themselves group to form even larger clusters?
These clusters don’t tend to aggregate further. Try a different Aβ?
Beta Amyloid 42 easily forms more stable clusters of 5 or 6, called a “paranucleus.” Will these paranuclei form even larger clusters?
Beta Amyloid 42 paranuclei cluster to form even larger aggregates of Beta Amyloid 42. Try a different Aβ?
Beta Amyloid 42 is probably more toxic than Beta Amyloid 40 because of its greater tendency to form clusters. It is the two water-repelling amino acids at the end of Beta Amyloid 42 that increase its attraction to itself and thus its tendency to aggregate.
Treatment Target: The higher toxicity of clusters of Beta Amyloid 42 opens up two treatment targets. The first is to alter the enzyme that creates Beta Amyloid so that it creates Beta Amyloid 40 instead of Beta Amyloid 42. The second is to use molecules that interfere with the Beta Amyloid 42 - Beta Amyloid 42 attraction and thus reduce its tendency to cluster.