Disclaimer: all information given is based on recent research; some information presented is not concrete yet.
If you have seen or read about someone with Alzheimer's, you may observe a slow deterioration in memory and brain function.
What causes that?
Research shows that amyloid plaques and neurofibrillary tangles are possibly the reason for the loss or damage of neurons that can cause Alzheimer's.
What are Amyloid Plaques?
There is a protein named amyloid precursor protein (APP) that is embedded in the cell membrane of a brain neuron and is used to develop and fix neurons[3].
Usually, the protein has to break apart to become recycled. An enzyme called alpha secretase (α secretase) and gamma secretase (γ secretase) splits the precursor protein into soluble fragments (fragments that can be dissolved).
This pathway is called the non-amyloidogenic pathway, meaning that it does not produce the detrimental plaques in the process:
However, there is an alternative pathway called the amyloidogenic pathway[2]. In this process, instead of alpha secretase, beta secretase (β secretase) and gamma secretase cuts up the precursor protein, resulting in an insoluble fragment called amyloid beta (Aβ)[1]:
As you can see, the typical, non-amyloidogenic pathway creates soluble fragments, in which we call the protein to be in its native state[1].
On the other hand, the amyloidogenic pathway creates the insoluble, amyloid beta fragments.
The amyloidogenic pathway has a more negative Gibbs free energy (ΔG˚) than the regular pathway, indicating that it is more likely to take this path given the trigger of certain environmental factors, mutations, etc[2].
[if you don't know what Gibbs free energy is, it basically means the more negative, the more likely its going to happen]:
Going back to the amyloidogenic pathway, these amyloid beta fragments clump up in extracellular environments, blocking neuron-to-neuron signalling, or signal transduction, and causing proneness from disease from inflammation[3].
The clumping can also lead to Amyloid Angiopathy where they clump near blood vessels and cause hemorrhage[3].
What are Neurofibrillary Tangles?
Beta amyloid clumps can also trigger intracellular (in-cell) pathways in neurons, causing tau proteins that hold microtubules together to clump, breaking the structure of the microtubule[1].
The clumps are called neurofibrillary tangles:
Overall, both plaques and tangles assist in the deterioration of neurons, and thus also contribute to neurodegenerative diseases such as Alzheimer's.
There is still many things yet to be discovered about Alzheimer's, and hopefully, more research can be done in the future.
I hope this blog was informative; happy studying!
Glossary (Bolded):
Amyloid Plaques: Clumps of Amyloid beta fragments that can prove detrimental to cell signaling.
Neurofibrillary Tangle: Clumps of tau proteins
Amyloid Precursor Protein (APP): Protein embedded within the cell double phospholipid bilayer, also known as an integral membrane protein
Alpha secretase (α secretase): Enzyme that assists in cleaving APP
Gamma secretase (γ secretase): Enzyme that assists in cleaving APP
Soluble Fragments: Fragments that can dissolve
Non-amyloidogenic: pathway of cleaving APP that does not result in amyloid beta.
Amyloidogenic: pathway of cleaving APP that does result in amyloid beta.
Beta secretase (β secretase): Enzyme that assists in cleaving APP
Amyloid beta (Aβ): the insoluble result of the amyloidogenic pathway, creating a very stable conformation (protein folding).
Native State: The state of the protein that is properly folded
Gibbs free energy: Energy able to do work
Extracellular: Out of cell
Signal Transduction: cell-to-cell signaling (more on this later)
Amyloid Angiopathy: Amyloid build-up on arteries that can result into bleeding.
Intracellular: Inside of cell
Tau Proteins: Proteins that hold together and stabilize microtubules
Microtubules: "tubes" inside cells that assist with transporting nutrients.
References:
1. Cole, Sarah L, and Robert Vassar. “The Alzheimer's Disease β-Secretase Enzyme, BACE1.” Molecular Neurodegeneration, BioMed Central, 1 Jan. 1991, molecularneurodegeneration.biomedcentral.com/articles/10.1186/1750-1326-2-22.
2. Eisenberg, David, and Mathias Jucker. “The Amyloid State of Proteins in Human Diseases.” Cell, U.S. National Library of Medicine, 16 Mar. 2012, www.ncbi.nlm.nih.gov/pmc/articles/PMC3353745/.
3. Osmosis. “Alzheimer's disease - plaques, tangles, causes, symptoms & pathology.” YouTube, 22 Mar. 2016, https://www.youtube.com/watch?v=v5gdH_Hydes&t=217s.
(sorry about the formatting of the references)
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