THE CANADIAN JOURNAL OF NEUROLOGICAL SCIENCES Detection of Lewy Bodies in Trisomy 21 (Down's Syndrome)

The presence of cortical senile plaques and neurofibrillary tangles sufficient to warrant a neuropathological diagnosis of Alzheimer's disease is well established in middle-aged individuals with Trisomy 21 (Down's syndrome). In contrast a relationship between Down's syndrome and Lewy bodies, one of the major neuropathological features of Parkinson's disease, has not been previously reported. In a cliniconeuropathological survey of 23 cases of Down's Syndrome, two patients, aged 50 and 56 years respectively, were found to have Lewy body formation in the substantia nigra in addition to cortical Alzheimer-type pathology. Neither case showed significant substantia nigra neuron loss although locus coeruleus loss was present in both. Since substantia nigra Lewy bodies are a characteristic neurohistological feature of idiopathic Parkinson's disease, their occurrence in cases of Down's syndrome with evidence of Alzheimer-type pathology supports an aetiopathological connection between Parkinson's disease, Alzheimer's disease, and Down's syndrome; and suggests that common pathogenic mechanisms may underlie aspects of neuronal degeneration in these three disorders, some of which may relate to aberrant chromosome 21 expression. RESUME: Detection de corps de Lewy dans la trisomie 21 (syndrome de Down). La presence de plaques seniles corticales et d'amas neurofibrillaires en quantite suffisante pour justifier un diagnostic neuropathologique de maladie d'Alzheimer est bien etablie chez les individus d'age moyen porteurs de la trisomie 21 (syndrome de Down). Par contre, une relation entre le syndrome de Down et les corps de Lewy, une des manifestations neuropathologiques majeures de la maladie de Parkinson, n'a jamais ete rapportee dans le passe. Dans une etude cliniconeuropathologique de 12 cas de syndrome de Down, des corps de Lewy ont ete retrouves dans la substance noire de deux patients ages respectivement de 50 et 56 ans, qui avaient egalement des manifestations anatomopathologiques corticales de type Alzheimer. Aucun de ces cas n'avait de perte neuronale significative au niveau de la substance noire, bien qu'il y eut des pertes neuronales dans le locus coeruleus chez les deux patients. Comme les corps de Lewy de la substance noire sont une manifestation neurohistologique caracteristique de la maladie de Parkinson, leur existence chez des cas de syndrome de Down avec evidence de pathologie de type Alzheimer supporte qu'il y ait un lien etiopathologique entre la maladie de Parkinson, la maladie d'Alzheimer et le syndrome de Down et suggere que des mecanismes pathogeniques communs pourraient etre a la base de certains aspects de la degenerescence neuronale dans ces trois affections, possiblement en relation avec une expression anormale du chromosome 21. Can. J. Neurol. Sci. 1993; 20:48-51 It is well established that most middle-aged individuals with trisomy 21 (Down's Syndrome) develop neuropathological abnormalities characteristic of Alzheimer's Disease — cortical senile plaques and neurofibrillary tangle formation — which are usually accompanied by a decline in mental function." Many similarities have been demonstrated between Alzheimer's Disease and Down's syndrome from clinical, neuropathological, and neurochemical viewpoints. The finding of a common cerebral amyloid protein (p-A4) in cortical plaques in both conditions, derived from a common precursor molecule (Amyloid Precursor Protein — APP) which maps to chromosome 21, has reinforced an association between these two disorders. Although Lewy body inclusions (accompanied by substantia nigra neuron loss) have been regarded as a hallmark of idiopathic Parkinson's disease, the recent identification of Lewy bodies in elderly demented individuals showing a pattern of Alzheimer-type pathology distinct from Alzheimer's disease — characterized by cortical plaque formation and amyloid deposition, but with few or absent neocortical tangles, and only moderate substantia nigra neuron loss" — has both enlarged the spectrum of Lewy body disease and emphasized an association between two of the major neurodegenerative diseases — Alzheimer's and From the Department of Neuropathology & MRC Neurochemical Pathology Unit, Newcastle General Hospital, Newcastle-upon-Tyne (R.R., A.B., D.I., P.G.I., R.H.P.); Northgate Hospital, Morpeth, Northumberland (C.K.-N., K.D.); Prudhoe Hospital, Prudhoe, Tyne and Wear (S.P.T.); Department of Psychiatry, University of Newcastle-upon-Tyne (K.D., S.P.T.), United Kingdom Received June 9, 1992. Accepted in final form September 1, 1992 Reprint requests to: Dr. R. Raghavan, Senior Registrar, Department of Neuropathology, Newcastle-upon-Tyne NE4 6BE, United Kingdom 48 https://www.cambridge.org/core/terms. https://doi.org/10.1017/S0317167100047405 Downloaded from https://www.cambridge.org/core. IP address: 54.191.40.80, on 21 Aug 2017 at 11:42:56, subject to the Cambridge Core terms of use, available at LE JOURNAL CANADIEN DES SCIENCES NEUROLOGIQUES Parkinson's disease." The possible association between neuropathological features of Alzheimer's and Parkinson's diseases prompted a neuropathological study to identify Lewy bodies in the brains of middle-aged cases of Down's syndrome. MATERIALS AND METHODS Brains were obtained from 23 individuals with Down's syndrome over the age of 30 (range 31-74 years) who had died in psychiatric institutions or those for the mentally handicapped in Northumberland. Cases derived from Northgate hospital had been prospectively assessed (CK-N) at regular intervals for evidence of deteriorating mental function and neurological impairment. Control cases (n = 20) were derived from age-matched patients dying in Newcastle General Hospital without any evidence of neurological or psychiatric disease. Table 1 shows the sex and age at death of these two groups. The diagnosis of Down's syndrome (of the trisomy 21 type) was based on clinical phenotypic features supplemented by confirmatory chromosome studies available in 17 cases. Neuropathological methods followed those established in Newcastle, senile or neuritic plaque density being quantified on frozen von Braunmuhl stained sections (25|i) and neurofibrillary tangles being assessed on paraffin embedded Palmgren-stained sections (20|i). Both frozen and paraffin tissue blocks were taken from standard areas in the four Table 1: Age (at Death) and Sex of 23 Individuals with Down's Syndrome