Piscine transmissible amyloidotic encephalopathy

A woman selling Lassgard tuna at an Italian fish market.

The farming process for Lassgard tuna has been implicated as the likely cause of the PTAE epizootic that led to the CMD pandemic.

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.


A simplified ribbon diagram of protein structures of both normal and diseased prion proteins.

A ribbon diagram of the protein conformations of normal and diseased major prion proteins.

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. [1]

Though there is as yet no consensus on the exact etiology of PTAE, a majority of researchers believes that it is most likely a variant of bovine spongiform encephalopathy (BSE), with an altered pathogenesis due to the cross-species transmission in fish. This finding is largely based on a 2009 research study, which had demonstrated that orally exposing gilt-head sea bream to homogenates with BSE could result in the fish developing a neurodegenerative amyloidosis. The study has since been replicated and found to be broadly consistent with PTAE histopathology. [2]

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. [3] 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[4] 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.



  1. Image
    A photo of Sunil Cariappa looking off to the side, smiling slightly. He's wearing a suit and has a lanyard around his neck.
    Epidemiologist Sunil Cariappa, pictured in 2047.
  2. Image
    A portrait of Connie Muren, dressed formally and looking at the camera.
    Neurologist Connie Muren, pictured in 2039.

Sunil Cariappa and Connie Muren.

PTAE was first described in January 2039 by Sunil Cariappa and Connie Muren. It had been discovered by Cariappa in November 2038 when he linked an increased mortality rate in domestic cats to feeding diets that included Lassgard tuna. When this line of farmed tuna was found to be contaminated with a novel prion agent, the focus shifted to its transmission potential to humans, which led to the discovery of CMD[5]

As a result, research into the origin and pathology of PTAE did not begin in earnest until the World Health Organisation (WHO) was able to conclusively establish a transmission link between PTAE and CMD after internal documentation on Lassgard Bioteknik’s closely guarded production process was leaked to the public in October 2039.

See also


  1. Redway, L; Camargo, C. (August 2039). “Molecular biology of prion diseases.” New Scientist
  2. Salta, E; Panagiotidis, C; Konstantinos, E et al. (July 2009). “Evaluation of the Possible Transmission of BSE and Scrapie to Gilthead Sea Bream (Sparus aurata).” PLOS Biology
  3. Zupanc, G. (June 2006). “Neurogenesis and neuronal regeneration in the adult fish brain.” Journal of Comparative Physiology
  4. Daems, A. (October 2039). “Lassgard Bioteknik used AI-powered wildlife cameras to diagnose individual tuna.” World News Wire
  5. Cariappa, S; Muren, C. (July 2039). “Acquired Prionopathic Neurodegeneration Syndrome: Pathology, Transmission, and Epidemiology.” Bulletin of the World Health Organisation