Transcript

Overview:

A digitally drawn comic in a muted color palate. The characters are all mice styled to look like people and wearing human clothes, the point of view character is a grandma mouse, usually wearing a dress, glasses, and a cardigan.

Cover:

Unseen Collapse: The Gradual Disintegration of Neural Networks in Alzheimer’s

Written by Dr. Mike Wehr and Zadie Niedergang.

Drawn by Zadie Niedergang

April, 2025

With thanks to the University of Oregon Comics and Science Initiative.

Cover description: A grandma mouse wearing glasses, a dress and a cardigan sits at a table holding a cup of tea.

Page 1:

Panel 1: The parking lot of “Fred Mousers’,” parked cars are made from wedges of cheese. Grandma mouse wears glasses and a cardigan as she pushes her cart and thinks, “Where am I?”

Panel 2: Grandma mouse sits in a doctor’s office with a concerned family member. The doctor explains, “Getting lost is a symptom of Alzheimer’s. There’s still no cure, but we can be here for you and your family.”

Panel 3: Grandma mouse sits at her kitchen table with a steaming cup of tea, thinking.

Panel 4: The panel is split into increasingly narrow vertical panels showing a sliver of grandma mouse, in the first panel we can see most of her head, but slowly our view narrows to just seeing her eye. She thinks, “am I going to lose myself? Lose my family? What’s going to happen to me?”

Page 2:

Panel 1: “As people age it’s normal to lose visual and auditory acuity and become more forgetful.” Grandma mouse reaches for a jar on a grocery store shelf.

Panel 2: Grandma mouse outside her front door carrying a grocery bag, walking with a cane. “With Alzheimer’s, memory issues keep getting worse and eventually become dangerous.

Panel 3: Grandma mouse stands on an iceberg. Most of the iceberg is below the surface of the water.

Panel 4-6: A sequence starting with a kettle on an electric stove. The burner is on, and the kettle is hot. “The disease actually starts decades before you notice symptoms.” The base of the kettle is engulfed in small flames. “By the time symptoms appear, damage to the brain is already irreversible.” The third panel is consumed in flames. “But what if we could detect Alzheimer’s earlier—with simple and non-invasive tests—before it’s too late?”

Page 3:

Panel 1: “Gap detection is the ability to detect silence between sounds.” A sound wave with bursts of noise punctuated with flat periods of silence streams into a person’s ear.

Panel 2: “In Alzheimer’s patients, gap detection is impaired much earlier than memory. But we still don’t know why.” Close up on a person’s ear, twitching at a noise.

Panel 3: A diagram of the brain highlighted sections that handle visual, auditory, speech, planning and interpretive tasks. “Our brains use complex neural networks to interpret sound.”

Panel 4: “Neurons fire, sending signals across the brain.” An illustrated of neurons, star-like cell bodies connect with long axons.

Page 4:

A full page spread shows an airplane traveling along many networked airpaths between hub airports on a map. “Signals travel through synaptic connections between neurons.  Like international airports connecting local airports across the country, so-called “hub neurons” act as key connection points, holding a fragile network together. We think Alzheimer’s slowly degrades neural networks for decades. The networks are resilient, compensating for damage, so patients show no symptoms. For Alzheimer’s patients, the tipping point is when hub neurons start failing and networks become disconnected. Only then do memory issues become noticeable to friends and family.”

Page 5:

Panel 1-3: “This is tied to the idea of “gradual degradation.” The theory that brain function degrades slowly and consistently over time. Researchers believe gradual degradation occurs until hub neurons fail.” In the first panel several neurons are connected in a network, in the second panel a few of the neurons go dark. In the third panel over half of the neurons are gone.

Panel 4: A mouse waves at a plane taking off. “When your flight is canceled and you lose access to the function associated with that hub neuron.”

Panel 5: a flow chart showing the progression of Alzheimer’s:

• Disease onset.
• Gradual degradation.
  • Gradual degradation can last years or decades, until hub neuron failure sets off a cascade, resulting in noticeable symptoms. Gap detection most likely starts to deteriorate during gradual degradation.
• Hub neuron failure.
• Noticeable symptoms
• Diagnosis: a grayscale view of grandma mouse sitting in the doctor’s office talking to her doctor.

Page 6:

A recreation of the flow chart on page 5: disease onset, gradual degradation, hub neuron failure, noticeable symptoms, diagnosis. An arrow indicates moving the diagnosis step to within gradual degradation “The goal of the Wehr Lab at the University of Oregon is to move diagnosis earlier.”

An instrument points a green laser at a mouse’s brain. “They are working to visualize and establish a link between hub neuron failure and gap detection. To visualize neural network breakdown they are using Alzheimer’s model mice and 2-photon microscopy.”

Page 7:

Panel 1: “The model mice (5XFAD) have been genetically engineered and bred to develop sever amyloid plaques, a physiological mirror of Alzheimer’s in humans.” A laser points at a diagram of a brain with plaques.

Panel 2: “The Wehr lab hypothesizes that gap detection degrades before hub neurons fail.”

Panel 3: “If this is true, gap detection would be a concrete biomarker of Alzheimer’s disease progression.”

Panel 4: On a desk in a lab, a mouse sits in an imaging machine with a laser pointing at its brain. “Physicians could use simple, non-invasive gap detection tests to help diagnose Alzheimer’s.”

Page 8:

“Thousands of scientists are working together to cure Alzheimer’s. Gap detection is just one small piece of the puzzle.” An interconnected network with grandma mouse at the center, connected to the NIH, academia, research, caretakers, pharmaceuticals, family and healthcare.