The diagnosis of the degenerative dementias relies on the identification of neuronal or glial inclusions made up of aggregated proteins. The taupathies probably constitute the largest group which includes Alzheimer’s and Pick’s diseases, diseases associated with mutations of the tau gene, progressive supranuclear palsy, corticobasal degeneration and argyrophilic grain disease. Lewy bodies, when numerous in the cerebral cortex, are usually associated with the cognitive deficit of the Parkinson’s disease dementia complex or of dementia with Lewy bodies – the conditions being distinguished by clinical data. Inclusions of the dentate gyrus that are labelled only by anti-ubiquitin antibodies are typical of a sub-group of fronto-temporal dementias that are sometimes familial and sometimes associated with amyotrophic lateral sclerosis. Mutations of the pre-granulin gene have been recently discovered in a significant proportion of these patients. Neuronal Intermediate Filament Inclusion Disease (NIFID) is a rare, apparently sporadic dementia characterised by the presence of large inclusions in the cell bodies of many neurons. These inclusions react with antibodies directed against neurofilaments or against other intermediate filaments (such as alpha-internexin). The diagnostic value of some of these inclusions as a basis for the classification of degenerative dementias has been challenged. The link between inclusions and pathogenetic mechanisms is probably quite variable. However, whenever the composition of inclusions has been elucidated, important clues to the pathogenesis of the disease in which they were found have been discovered.
© 2006 Elsevier Masson SAS. Tous droits réservés.