NR AAXA
AU Baker,H.F.; Ridley,R.M.; Wells,G.A.H.; Ironside,J.W.
TI Spontaneous spongiform encephalopathy in a monkey
QU Lancet 1996 Oct 5; 348(9032): 955-6
KZ Lancet. 1996 Jul 6;348(9019):55. PMID: 8691939
PT comment; letter
VT
SIR - The neuropathological lesion profile of the spongiform encephalopathy (SE) seen in animals naturally or experimentally infected with bovine SE (BSE) is uniform for each species.[1] The clinical and neuropathological picture after experimental transmission of BSE to three macaques has been described.[2] The spontaneous disease that Bons and colleagues (July 6, p 55)[3] report in a macaque in Montpelier zoo differs from this description both clinically and neuropathologically.
The monkey showed prolonged social and behavioural disturbance, whereas the signs associated with experimental SE in primates, including those infected with BSE,[2,4] are principally neurological, consisting of truncal ataxia, broadbased gait, poor balance, and a reluctance to release the hands from postural support, which is especially conspicuous when the animals are eating. These signs become debilitating and then life-threatening, usually over a period of weeks to months, although duration of illness may be as short as a few days or even hours. The pathological changes in the Montpelier monkey are recorded in the deep layers of cerebral cortex whereas, in BSE-infected primates, these changes are most intense in the thalamus and striatum. Although the description of the pathology in the Montpelier monkey is that of SE, the figures leave considerable doubt. They depict irregular histological spaces, with occasional indentations and traversing septae, suggestive of the intramyelinic vacuolation characteristic of spongiform leucoencephalopathies, which have various metabolic and toxic aetiologies. In our view the changes shown are not those of the vacuolated neurons of SE, as captioned.
The brains of BSE-infected macaques contained numerous, characteristically florid prion protein (PrP) plaques which could also be easily seen without immunostaining. No such structures are described in the Montpelier monkey. The illustrated PrP deposits do not resemble those seen in BSE[1] or in SE in any other species we have studied, including macaques and man. In the absence of data from a control animal or the results of staining with thioflavin S, the anti-ß-protein immunostaining in the neuropil in this 10-year-old monkey could be non-specific. Age-related ß-protein deposition is not seen in macaques less than 20 years old.[5] This monkey probably had a neurodegenerative disease unrelated to prion disease.
*Harry F Baker, Rosalind M Ridley, Gerald A H Wells, James W Ironside
*MRC Comparative Cognition Team, Department of Experimental Psychology, School of Clinical Veterinary Medicine, Cambridge CB3 OES, UK; Department of Pathology, Central Veterinary Laboratory, Addlestone; and National CJD Surveillance Unit, Western General Hospital, Edinburgh
1 Wells GAH, Wilesmith JW. The neuropathology and epidemiology of bovine spongiform encephalopathy. Brain Pathol 1995; 5: 91-103.
2 Lasmézas CI, Deslys J-P, Demaimay R, et al. BSE transmission to macaques. Natur 1996; 381: 743-44.
3 Bons N, Mestre-Francés N, Chaanay Y, Tagliavini F. Spontaneous spongiform encephalopathy in a young adult rhesus monkey. Lancet 1996; 348: 55.
4 Baker HF, Ridley BM, Wells GAH. Experimental transmission of BSE and scrapie to the common marmoset. Vet Rec 1993; 132: 403-06.
5 Struble RG, Price DL Jr, Cork L, Price DL. Senile plaques in cortex of aged normal monkeys. Brain Res 1985; 361: 267-75.
Author's reply
SIR - Baker and colleagues' main criticism is that the clinical and pathological features shown by the Montpellier monkey Macaca mulatta differed from those of cynomolgus monkey (Macaca fascicularis) experimentally infected with BSE. These differences raise questions on the nature and origin of the neurodegenerative disorder noted in the Montpellier monkey, since the lesion profile seen in animals naturally or experimentally infected with BSE is uniform within each species. We agree with this point of view. However, in our report we did not suggest a link to BSE; we advanced the possibility of transmission of the disease through prion-contaminated foodstuff, similar to that proposed for BSE. Thus, the two models (spontaneous degeneration without known cause versus intracerebral inoculation with BSE) are not readily comparable, and clinicopathological differences are conceivable.
The Montpellier monkey was not examined clinically in detail, and few data have been obtained from animal attendants. Presumably, the monkey showed neurological signs in addition to behavioural changes, since the involvement of the brain the pathological process was extensive, as specified below. Nevertheless, abnormal behavioural signs similar to those shown by our monkey (eg, edginess) have been also noted in the initial stage of the experimental spongiform encephalopathy of BSE-infected macaques.
With respect to the neuropathological features of the Montpellier monkey, spongiform changes were prominent in many grey structures, including the cerebral cortex, striatum, thalamus, and cerebellar cortex. Changes in the white matter were minor, and were related to enlargement of nerve-cell processes without demyelination. The spongiform changes were associated with PrP and ß-protein deposition.
In view of Baker and colleagues' concerns, we will undertake other immunohistochemical investigations (no frozen tissue is available for immunoblot analysis) with a large panel of antibodies to PrP. However, the labelling reported in the monkey was not shown in the lemurian primate (Microcebus murinus) species investigated in my laboratory. With respect to the ß-amyloid plaques, the results were obtained with several monoclonal and polyclonal antibodies, and with thioflavin S and PAM silver impregnation in three different laboratories (Montpellier, Bons; Boston, Mesulam; Milan, Tagliavini) and these results cannot be contested.
Noelle Bons
Ecole Practique Des Hautes Etudes, Laoratoire De Neuromorphologie. Fonctionelle, 34095 Montpellier, France
ZR 5 Zitate
MH Animal; *Macaca; Monkey Diseases/*pathology; Prion Diseases/pathology/*veterinary
SP englisch
PO England
OR Prion-Krankheiten 1