Alzheimer's is a neurodegenerative disease which is characterized by cognitive decline and the loss of ability to form short-term memories. The disease gradually progresses to affect all facets of life and is incredibly sad to watch helplessly as a loved one goes through the progression. This disease has struck my own family and I can imagine that many of you have seen what I have.

Biochemically, Alzheimer's is thought to occur at least party due to the accumulation of thick waxy plaques in the brain comprised of a protein called amyloid beta (Abeta). There have been (and are still) numerous research projects looking into better understanding the accumulation of this protein plaque and to develop drugs which would work to either prevent it from accumulating more or break up what has formed.

Today let us briefly discuss some work published in the journal Nature: Scientific Reports titled "Chronic treatment with a smart antioxidative nanoparticle for inhibition of amyloid plaque propagation in Tg2576 mouse model of Alzheimer’s disease". The first person to reply to this post stating "Monkey Monkey, Tree, Look At Me, I'm talking Nonsense!" Will be sent 2 SBD. In this work the authors were studying a new nanoparticulate compound with reducing properties that could potentially allow it to break down these Abeta plaques.

Image Source

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Briefly Tell Me About This Nanoparticle

The nanoparticle which they abbreviate (RNP^N) is actually a long polymer comprised of the compound (poly(ethylene glycol)-b-poly[4-(2,2,6,6-tetramethylpiperidine-1-oxyl)aminomethylstyrene]), this compound has a water loving part (poly(ethylene glycol) and a water hating part (the rest of it). This results in the polymer forming what is known as a mycelle which basically is a ball like structure where a bunch of the water hating tail groups point inward together, leaving the water loving part to be in contact with water on the outside of the ball. The compound breaks apart under acidic conditions (like the stomach) which allows it to be absorbed by the body, where it can again reform (our blood is non acidic). [2]

This compound has reductive properties (it can gobble up radical oxygen species, and acts as an antioxidant), and has previously been shown to have antioxidant activities in the brains of some mice! [3] Knowing this, the authors here wanted to test whether it might be useful against Abeta plaques.

What Did They Find?

The researchers were using a transgenic mouse which had the Alzheimer's causing Abeta protein overexpressed (meaning they artificially induced the protein to be in these mouse's brains in high concentrations). These mice have cognitive difficulties just like humans with Alzheimer's. Next they confirmed that their nano-particle could get into the brains of these mice as had been previously shown for a different variety of mouse, and saw that yes it could. Okay step one, check, compound gets to the mouse brain...but does it do any good?

In this first test, mice were acclimated to a box containing an object in a particular position (in one corner). The mouse was removed, the object was moved, and the mouse was placed back in. Now mice are pretty smart, and they notice when something has changed in the environment and will go explore what has changed. Well unless they have alzheimers, then they can't remember and no longer spend time exploring. This test reports the difference in time that the mice spent exploring the change in object location allowing us to see what effect the compound had.

The important part to compare is first the wild type (non Alzheimers mice) vs the AD + Water group (alzheimers mice given water to drink). We see that the wild type mice spent much more time exploring the objects new location then the alzheimers mice (which spent no time... I guess they forgot). Next look to the bar showing AD + RNP^N this is the alzheimers mouse treated by their nano-particle. You can see that the nanoparticle greatly improved the mice's curiocity for the objects new location vs the AD + water group!

Other Article Observations (The "Brief" Rundown!)

• RNP^N improved the alzheimers mice's abilities to navigate their way to an invisible platform in a pool of water in the "Morris Water Maze test."
• Expression of proteins indicative of oxidative stress (known to be high in the alzheimers mouse) were significantly reduced upon treatment with the RNP^N nanoparticle.
• Decreased levels of both forms of Abeta (1-40) and (1-42) were observed in the brains of the alzheimers mice given RNP^N treatment. (1-42 is the form of the protein that typically forms the aggregate, seeing a reduction in the amount present in the mouse brains is very promising).

Conclusions

The authors report that their nanoparticle (RNP^N) which has the ability to break down in the stomach, easily get absorbed, re-assemble and get to the brain. Also has antioxidative properties, reduced the amount of amyloid beta in a mouse model, as well as helped those mice regain some cognitive functioning. A very interesting and promising piece of work!

Sources

1. https://www.nature.com/articles/s41598-017-03411-7
2. http://pubs.acs.org/doi/abs/10.1021/bc900214f
3. http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0126013

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