Thu, 2019-10-17 15:51 -- Anonymous (not verified)
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Letter to the Editor

Alzheimer’s and dolphins

Giovanni DI GUARDO, DVM, Dipl. ECVP,
Professor of General Pathology and Veterinary Pathophysiology,
University of Teramo, Faculty of Veterinary Medicine, 64100 - Teramo, Italy
(Email address: gdiguardo@unite.it)

Alzheimer’s disease (AD), the most common type of dementia on a global scale, is still in search of reliable animal models faithfully recapitulating its key neuropathological features, i.e. amyloid ß (Aß) deposition and neurofibrillary tau protein tangles, in diseased human brains (1). In this respect, while the demonstration of Aß dimer-induced glutamergic neuron dysfunction reported in murine models by Benedikt Zott and coworkers (2) is noteworthy, it should be also emphasized that Aß and tau aggregates have been simultaneously detected in the brain of stranded bottlenose (Tursiops truncatus) and striped dolphins (Stenella coeruleoalba) (3). Furthermore, Aß plaque-associated cerebral pathology has been recently documented in bottlenose dolphins stranded along the Atlantic USA coastline, with their brain tissue also harboring high concentrations of β-methylamino-L-alanine (BMAA), a cyanobacterial neurotoxin (4).
Can these findings, that are totally unprecedented in cetaceans and, more in general, in any wild animal species, “candidate” dolphins as valuable models for the comparative neuropathological and neuropathogenetic study of AD in mankind? This question should be preceded by an even more crucial one: are dolphins prone to develop AD, or any AD-like neuropathy? The answer is blowing in the wind!
Indeed, besides the fact this could impact the health and conservation of our incresingly threatened cetaceans worldwide, it should be additionally underlined that the host’s cellular prion protein (PrPC) acts as a pivotal neuron cell receptor for Aß, with PrPC-Aß interaction mediating the synaptic dysfunction(s) commonly seen in AD-affected individuals (5). Should similar PrPC-Aß relationships occur also in the brain tissue from striped and/or bottlenose dolphins, this would candidate them as potentially reliable models for the study of human AD and AD-like conditions (6). Nevertheless, despite their undeniable interest, such studies may be hampered by the compromised post mortem preservation degree in which stranded cetaceans are often found.

References

1. Querfurth, H.W. & LaFerla, F.M. Alzheimer's disease. N. Engl. J. Med. 362, 329-344 (2010).
2. Zott, B., et al. A vicious cycle of ß amyloid-dependent neuronal hyperactivation. Science 365, 559-565 (2019).
3. Gunn-Moore, D., Kaidanovich-Beilin, O., Gallego Iradi, M.C., Gunn-Moore, F. & Lovestone, S. Alzheimer's disease in humans and other animals: A consequence of postreproductive life span and longevity rather than aging. Alzheimers Dement. 14, 195-204 (2018).
4. Davis, D.A., et al. Cyanobacterial neurotoxin BMAA and brain pathology in stranded dolphins. PLoS One 14(3), e0213346; doi: 10.1371/journal.pone.0213346 (2019).
5. Lauren, J., Gimbel, D.A., Nygaard, H.B., Gilbert, J.W. & Strittmatter, S.M. Cellular prion protein mediates impairment of synaptic plasticity by amyloid-β oligomers. Nature 457, 1128-1132 (2009).
6. Di Guardo, G. Alzheimer’s disease, cellular prion protein, and dolphins. Alzheimers Dement. 14, 259-260 (2018).

No competing Interests: 
Yes
The following competing Interests: 
Electronic Publication Date: 
Thursday, October 17, 2019 - 15:44
Workflow State: 
Released
Contributors: 
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Full Title: 

Alzheimer’s and dolphins

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