What is happening in 35 million brains across the globe because of Alzheimer's Disease?

While brainstorming what to research for a blog post, I tried to focus on diseases that interested me but also those with which I had personal connections to.  So I came across an article that talked about Alzheimer’s disease (AD) called “Brain insulin signaling, glucose metabolism and female’s reproductive aging: A dangerous triad in Alzheimer’s disease.”  According to this article, AD is the main cause of dementia and impacts approximately thirty-five million people across the globe, and ⅔ of these are women (Duarte, Santos, Oliveira, & Moreira, 2018).  After the age of sixty-five, women are much more likely to develop behavioral and cognitive changes than men.  This means that old age and being female are two risk factors for AD, which is slightly terrifying since I am a female and will (hopefully) continue to age for a while.  Alzheimer’s is a neurodegenerative disease that beings with “subtle decline in the ability to encode new memories,” then progresses towards profound behavioral, cognitive, personality, and adaptive deterioration (Duarte, Santos, Oliveira, & Moreira, 2018).  Sooner or later, those with Alzheimer’s forget what they ate for breakfast the previous day, who they live with, and even their families.

Here is a little background on Alzheimer’s disease and its characterizations.  AD is characterized mainly by extracellular senile plaques (SPs) formed by amyloid build-up in the brain.  These plaques mostly contain amyloid-beta (AB), which has 40-42 amino acids.  This amyloid-beta comes from the processing of the amyloid-beta precursor protein (ABPP), which is then catalyzed by aspartic protease beta-site ABPP cleaving enzyme-1 and then by gamma-secretase complex.  Interestingly, AB impairs hormone-mediated signaling (including estrogen and insulin), mitochondrial metabolism, and calcium homeostasis, which leads to stress laid on the endoplasmic reticulum, microglia activation and inflammation, and endothelial dysfunction.  This all leads to synaptic and cognitive loss (Duarte, Santos, Oliveira, & Moreira, 2018).  But AB that has yet to aggregate may also act as an infectious agent and can move in neurons and across synapses from the neocortex to other regions in the brain, allowing the plaque-forming ability to spread as well (Duarte, Santos, Oliveira, & Moreira, 2018).

            AD is also characterized by intracellular neurofibrillary tangles (NFTs).  NFTs are composed of helical filaments that contain the aggregated hyperphosphorylated Tau protein.  The Tau protein is of the family of microtubule-associated proteins (MAPs) that interact with tubulin.  They help maintain the axonal diameter and the stability of the microtubules to essentially maintain the structure of the neurons and the transport of the synapses.  If Tau aggregates in neuronal perikaryal, it interferes with the network of microtubules and induces stress on oxidation and causes the mitochondria to malfunction, which can cause neurodegeneration and neural death.  AB, the amyloid-beta, can induce Tau to aggregate, which only causes these negative effects to worsen (Duarte, Santos, Oliveira, & Moreira, 2018).

            The last characterization of AD is a downregulation of both pre- and post-synaptic proteins.  This causes neurodegeneration and neural death, which causes cognitive deficiencies as well (Duarte, Santos, Oliveira, & Moreira, 2018).

AD is extremely interesting, but is such an awful, heartbreaking disease.  My father’s grandmother, who is still alive and kicking at 101 years old, has AD, and she has no idea who any of her five children are.  If I went to visit her today, she would not remember me or my family, and that saddens me.  I cannot imagine not remembering my family, and watching my grandfather talk to his mother and seeing how she does not know who he is is tragic.  I never want to become part of the 35 million people in the world that gets AD, but I know how it feels to have a family member go through the loss of memory, cognition, and relationships.  So while AD is extremely interesting, it is not something I hope to become more personally familiar with.

References

Duarte, A., Santos, M., Oliveira, C., & Moreira, P. (2018). Brain insulin signaling, glucose metabolism and females reproductive aging: A dangerous triad in Alzheimer’s disease. Neuropharmacology. doi:10.1016/j.neuropharm.2018.01.044