Chapter 1 – The Tau Theory  
"Woah! Where am I?" asked Tau as he peered around  
in the distance.  
Tau was inside an axon, sitting on a microtubule. He  
looked at the microtubule with fascination. It was a  
long, no, really long cylindrical fiber atop which he was  
perched.  
It was like a train track, he thought, but floating, and in  
the distance, if he peered far enough, he could see  
something. That something was a motor protein –  
walking along his microtubule!  
"Hey there, Tau!" said his microtubule. Tau jumped in  
surprise. "You can talk?!" he exclaimed. "Well, yeah,  
I'm kind of like you, you're a protein, and I'm just a  
bunch of proteins."  
Tau was a young protein. He'd just gained consciousness, but he has a crucial role in  
our cells. He provides structural integrity to microtubules (our cellular rail tracks) and  
holds them together. Without Tau, this vital transport mechanism would collapse.  
"What am I supposed to do?" asked an inquisitive Tau. "Nothing new for now. Just hold  
all of us together," smiled the microtubule. "When a motor protein comes along, kinases  
will come to move you out of the way."  
"Wait, what are motor proteins?" asked Tau.  
"Motor proteins are like trains running along microtubules. They 'walk' along  
microtubules and transport essential cellular cargo from one end of the cell to another.  
We’d not be able to function without them."  
"So why do I need to move out of the way when motor proteins come along?"  
"I'll let the kinases explain."  
"Hey there, Tau!" shouted a group of friendly-looking proteins who came towards Tau.  
"Hi! Are you guys the kinases?"  
"I see you've heard about us already! But I like to call ourselves the pit crew. We come  
and get you ready to leave your microtubule, so you don't block the path for the motor  
protein."  
Tau watched in fascination as the kinases came and attached a bunch of phosphate  
groups onto him. He looked so different. He was ... phosphorylated!  
This caused him to detach from his microtubule and float around in the axon.  
Everything was so new to him, but he was filled  
with awe as he watched the neuron's internal  
components work like clockwork. He was in a  
tiny cell, but it felt like a marvel of architecture –  
like a Frank Lloyd Wright building. There were a  
bunch of proteins that were around the edges of  
the cell and held the whole thing together – the  
cytoskeleton. There were proteins on the  
surface that so intricately managed the  
concentrations of contents inside and outside  
the cell. Then there were those with whom he  
interacted – the microtubule railway tracks, and  
proteins who walked along them. It was awe-  
inspiring to see how things that were essentially  
bundles of inanimate molecules had an  
emergent property of being alive!  
"Tau! Tau! Did you fall asleep?!" asked a  
phosphatase as Tau broke out of his reverie.  
"No! Just thinking," Tau replied. "Who are you?"  
"I'm a phosphatase," said the phosphatase. "I'm here to remove your phosphate groups  
and send you back to your original shape – so you can go and hold the microtubules  
together!"  
Again, Tau watched in fascination as phosphatase chopped away at his phosphorylated  
ends. The cell was such a mesmerizing display of coordination and activity.  
Chapter 2 – Tau's Rebellion  
Years passed, and Tau continued this cycle day in and day out. He relentlessly held the  
microtubules together, listened obediently as the kinases and phosphatases moderated  
his functioning by phosphorylation. All systems worked like clockwork.  
Unfortunately, Tau was now a teenage protein, and just like all teenage proteins, he was  
vulnerable to rebellions, mood swings, and peer pressure.  
So, as Tau woke up one day, he felt different. He'd changed intrinsically. Through a  
mutation in his gene, he was more prone to becoming hyperphosphorylated.  
Everything seemed normal as the kinases arrived, but something was wrong with the  
kinases today. There were too many of them!  
"Whoa! Why are there so many of you today?" Tau asked, but didn't receive a reply.  
As the kinases bound to Tau and started  
phosphorylation, Tau could sense something  
was wrong, but with each increasing  
phosphate group, he just felt braver, more  
rebellious, and angrier! He now felt a strong  
urge to leave his microtubule, for he did all  
the work anyway! Why should he care for  
someone who never did anything for him? He  
felt hatred toward his neuron. He did all of the  
heavy lifting, he seemed to think, but the  
neuron never noticed!  
'I should leave them for good,' he thought.  
Just as we teens have our mood swings with  
our hormones, Tau had his, but due to  
hyperphosphorylation.  
Once the kinases were done with their work, Tau sped off – a misfolded, incorrectly  
functioning version of Tau, who didn't even care for his microtubule and neuron.  
Tau had become a rebel, a renegade protein, who stopped working as he was  
supposed to. Just as we can, proteins can get into a ton of bad habits, and there are so  
many avenues for them – some being an urge of rebellion (mutation) and peer pressure  
(upregulation of kinases and downregulation of phosphatases). In addition, other  
indirect processes, such as the accumulation of reactive oxygen species, beta-amyloid-  
mediated toxicity, and neuronal inflammation, can also cause the misfolding of Tau.  
Chapter 3 – A Renegade Tau epidemic  
Tau was drifting aimlessly, in his hyperphosphorylated, misfolded, and rebellious state,  
with no sense of purpose.  
As he was on his journey of 'self-discovery', our Tau bumped into a bunch of other rebel,  
misfolded Taus who formed a group called a 'pretangle'.  
"What's up, Tau?" they asked. "Care to join us?"  
Tau gladly obliged. He felt like he was in heaven! 'Another group of rebels? This is  
great!' he thought.  
"So what do y'all do?" Tau asked.  
"Oh, we just try to disrupt our neurons  
as much as we can. We try to form  
bigger and bigger groups of the  
'cooler' Tau rebels, I mean, who even  
wants to be associated with their  
microtubule!"  
"Oh yeah, of course," Tau relented.  
And as time passed, their cohort grew  
bigger. Many free-floating, misfolded  
Tau accelerated the formation of these  
protein tangles, initially forming sub-  
clans of Tau called "Paired Helical  
Filaments(PHFs)" - which self-  
constructed into larger Tau complexes  
called "Neurofibrillary Tangles(NFTs)".  
Chapter 4 – The Warzone Neuron  
"HA! That's what you get!" a member of Tau's NFT shouted as a microtubule fell apart.  
Microtubules need Tau to stay intact, and without them, they lose their structural  
integrity.  
"Let's wreck some more havoc!" shouted another member, to which all agreed gleefully.  
As Tau was about to leave with his NFT, he realized something – that microtubule that  
was falling apart was his. His neuron and his microtubule had started to disintegrate  
without him.  
He clung to the microtubule, trying desperately to hold it together.  
The microtubule smiled pensively at him one last time - "There's nothing you can do  
now", and vanished – disintegrating into tiny microtubule fragments.  
Tau looked around, and the whole neuron looked like a war zone. Multiple bunches of  
Tau NFTs floated around, obstructing the cell's critical functioning. Without microtubules  
and motor proteins, essential substances and organelles couldn't get from one end to  
the other. As Tau stopped binding to microtubules and the cell's cytoskeleton, the cell  
began disintegrating – with its foundation torn apart.  
The NFTs weren't just stopping there. They attracted more Taus to join them and  
blocked the path of essential molecules trying to move from here to there.  
The neuron was falling apart, Tau realized. There was nothing to be done, other than sit  
and watch as the neuron went up in flames.  
Chapter 5 – Conclusion  
An estimated 7.2 million Americans age 65 and older are living with Alzheimer’s disease  
and dementia in 2025 (Alzheimer’s Association, 2025, p.29). Alzheimer's impairs  
memory, learning, and other cognitive functions. The mechanism of Tau represents one  
possible theory for Alzheimer's cause, but the whole story is not yet fully understood,  
and Alzheimer's is most likely caused by a variety of genetic, physiological, and lifestyle  
factors. Not only do patients suffer from this mentally debilitating disease, but families  
are also affected, be it emotionally or financially.  
Treating and learning more about Alzheimer's and other neurodegenerative diseases  
holds the key to the betterment of tens of millions of lives.  
#researchsaveslives  
-Aryaman Deshmukh  
Bibliography  
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neurodegeneration in Alzheimer's disease and related disorders. In Nature Reviews  
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Congdon, E. E., Ji, C., Tetlow, A. M., Jiang, Y., & Sigurdsson, E. M. (2023). Tau-  
targeting therapies for Alzheimer's disease: current status and future directions. In  
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doi.org/10.1038/s41582-023-00883-2  
Medeiros, R., Baglietto-Vargas, D., & Laferla, F. M. (2011). The Role of Tau in  
Alzheimer's Disease and Related Disorders. In CNS Neuroscience and Therapeutics  
(Vol. 17, Issue 5, pp. 514–524). https://doi.org/10.1111/j.1755-5949.2010.00177.x  
TED-Ed. (2024, July 30). Why is Alzheimer's disease so difficult to treat? - Krishna  
Sudhir [Video] https://youtu.be/oT5pDvdMzhk  
Alzheimer’s Association. (2025). 2025 Alzheimer’s Disease Facts and Figures (Vol. 21,  
No. 5). Alzheimer’s & Dementia. Retrieved from https://www.alz.org/getmedia/ef8f48f9-  
ad36-48ea-87f9-b74034635c1e/alzheimers-facts-and-figures.pdf  
All images are generated using AI (ChatGPT).  
Acknowledgements  
I thank Johns Hopkins University for allowing me to partake in the Neurobiology :  
Cellular and Systems summer course. I also extend my gratitude to my instructor Dr.  
Preeti Vyas, and the TA, Mr. Javier-Rosado-Franco for invaluable feedback and  
guidance throughout the entire course.