April 26, 2023

Carter Hoskins, Dave Achonu, Jacob Moran

11th Grade

Baldwin Senior High School

Have you ever wondered what drives the Joker, the iconic villain from DC Comics, to his maniacal behavior? In the video game “Arkham Knight,” the Joker suffers from a mutated version of a rare and fatal neurological disorder known as Creutzfeldt-Jakob disease. If you haven’t heard of this disease, don’t fret; it doesn’t take a caped crusader to understand this disorder.

Although the video game depiction of Creutzfeldt-Jakob disease is merely fictional, it did get one thing correct: Creutzfeldt-Jakob disease is likely caused by abnormally shaped proteins, or prions. This process contributes to the formation of prion aggregates—harmful clumps of protein—that damage the brain and results in a slew of neurological complications.

Though Creutzfeldt-Jakob disease doesn’t result in villainous hysteria, its symptoms can seem like the work of evil. When highlighting the hallmarks of Creutzfeldt-Jakob disease, experts often compare it to Alzheimer’s disease, due to its familiarity with the general population. While patients of both disorders exhibit similar symptoms, the physical manifestations of Creutzfeldt-Jakob disease are often greater in magnitude. Stanford Medicine describes the complications associated with this disorder as memory impairment, cognitive decline, personality alterations, and compromised musculoskeletal control. In some rare cases, Creutzfeldt-Jakob disease can result in pathological laughing, reminiscent of the Joker’s infamous cackle. These symptoms develop swiftly, resulting in more severe complications, such as falling into a comatose state and eventually death.

At this point, you may be wondering how this disease develops; fortunately, it has nothing to do with criminal clowns. The mechanisms of Creutzfeldt-Jakob disease and other prion disorders are not yet fully understood by experts in the field. However, neurologists theorize that prion disorders develop as a result of misfolded proteins in the cerebrum.

Misshapen proteins, or prions, induce nearby, unsuspecting healthy proteins to adopt their abnormal structure. These irregular proteins rapidly proliferate, infecting more, otherwise healthy proteins, like a zombie apocalypse on the molecular level. The infected protein conglomerate forms harmful aggregates in the brain and wreaks havoc. According to neurologist Stanley Prusiner, these aggregates “accumulate primarily in the cerebral cortex,” the region of the brain responsible for memory, critical thinking, and personality. These physiological changes are responsible for the characteristic symptoms of Creutzfeldt-Jakob disease.

Currently, there is no cure or reliable preventative methods for prion diseases, and treatment interventions are limited to symptomatic relief. Although Creutzfeldt-Jakob disease is a rare disorder, researching this affliction is vital. Creutzfeldt-Jakob disease is part of a large group of neurodegenerative disorders caused by abnormal protein aggregates, including Alzheimer’s disease and Parkinson’s disease. According to biochemist Yusuf Tutar, “millions of people are affected [by] these diseases.” Studying disorders such as Creutzfeldt-Jakob disease allows for a greater understanding of these diseases and will pave the way toward discovering treatments, impacting the lives of millions. While the Joker's madness may be fictional, and the likelihood of Creutzfeldt-Jakob disease mutating into a Joker-esque disease is minuscule, the real-world implications of protein aggregate diseases are all too real, and understanding these conditions is crucial to developing effective treatments.