Piscine transmissible amyloidotic encephalopathy (PTAE), more commonly known as mad fish disease, is a neurodegenerative disorder that affects the central nervous system of fish. It has to date been described only in farmed tuna developed by Lassgard Bioteknik, though a 2009 study has previously established PTAE infections in gilt-head sea bream.
The transmission of PTAE to humans, primarily via ingestion of infected fish, can result in Cariappa-Muren disease (CMD). Although PTAE entered the food chain in 2034, it went undiscovered until the first cases of CMD were reported in 2039. Since PTAE-affected tuna are considered to be the primary infection vector for the CMD pandemic, it precipitated a dramatic overhaul of food safety regulations and the collapse of the aquaculture industry.
Piscine transmissible amyloidotic encephalopathy (PTAE) is classified as a transmissible spongiform encephalopathy (TSE) because its causative agent is considered to be a misfolded protein known as a prion. In the brain, these prions cause the native isoform of major prion proteins (designated as PrPc) to misfold into the same infectious state (designated as PrPSc), which goes on to convert further PrPc in an exponential cascade. This results in dense protein aggregates in the form of amyloid fibres that disrupt the normal tissue structure. 
Signs and symptoms
Fish infected with PTAE will not show any immediate symptoms due to the disease’s long incubation period. The clinical period is further delayed due to the significant potential for neurogenesis in fish.  It is thought that the conversion of PrPc into PrPSc is countered, though not outpaced, by the fish brain’s capacity for regenerating a variety of tissues and complete neuronal diversity.
Once the clinical period begins, erratic swimming and behavioural abnormalities will become apparent and grow progressively worse. Death usually follows the onset of hypokinesia, which prevents fish from maintaining the swimming behaviour required to keep pumping water through their gills. Caged fish, as with aquaculture farming sites, have also been known to kill themselves by swimming into walls and nets as a result of ataxia.  Given the challenging nature of accurately determining anomalous behaviour in individual fish, neuropathological and immunohistochemical examinations of post-mortem brain tissue remain the most reliable diagnosis method of PTAE.
- Redway, L; Camargo, C. (August 2039). “Molecular biology of prion diseases.” New Scientist. ↩
- Zupanc, G. (June 2006). “Neurogenesis and neuronal regeneration in the adult fish brain.” Journal of Comparative Physiology. ↩
- Daems, A. (October 2039). “Lassgard Bioteknik used AI-powered wildlife cameras to diagnose individual tuna.” World News Wire. ↩