, Volume 80, Issue 3, pp 318-327

The prevalence of amyloid (A4) protein deposits within the cerebral and cerebellar cortex in Down's syndrome and Alzheimer's disease

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Summary

The extent of amyloid deposition within the cerebellum and the cerebral cortex was assessed and compared, using anti-amyloid protein (A4) immunostaining and a novel methenamine silver method, in 20 patients aged between 60 and 77 years with Alzheimer's disease (AD), 29 patients aged between 13 and 71 years with Down's syndrome (DS), 26 demented patients with disorders other than AD and DS and in 20 non-demented elderly individuals of age range 60–102 years. In AD, amyloid deposits were noted in the cerebellar cortex in 90% of patients and in the meningeal vessels of the cerebellum in 80% of patients. In DS, amyloid deposits were seen in the cerebellar cortex in 82% of patients over 30 years of age and was universal in patients over 50 years of age. Overall, in DS, amyloid deposits were present in the meningeal vessels of the cerebellum in 79% of patients, but were present in 94% of those patients over 50 years of age. The sites of amyloid deposition in the cerebellar cortex were (poorly) detected by lectin histochemistry (Concanavalin A binding) in only 40% of patients with AD and 43% of all patients with DS (69% of those over 50 years of age). No amyloid deposits were seen in either the cerebellar cortex or its meningeal vessels in any of the 20 non-demented elderly individuals nor in any of the non-Alzheimer demented patients. The cerebellar amyloid deposits were never associated with a neuritic change [i.e. as characterised by the presence of (taupositive) paired helical filaments (PHF)] and neurofibrillary tangles were seen only in a few cells of the dentate nucleus in a single patient with AD and in three of the elderly DS patients. Amyloid deposits were numerous in the cerebral cortex of all patients with AD and in all, except the 13-year-old patient, with DS. In all the AD patients and in most of the DS patients over 30 years of age, many of the cerebral cortical amyloid deposits were associated with neurites and were strongly recognised by lectin histochemistry. Amyloid deposits were present within the meningeal vessels of the cerebral cortex in 75% patients with AD and 72% of patients, over 30 years of age, with DS (82% of those over 50 years of age). These data indicate that the process of amyloidosis in AD and in elderly DS patients is not restricted to the cerebral cortex and may affect other grey matter regions, particularly the cerebellum. However, it seems to be only in the cerebral cortex that such deposits are widely associated with a ‘reactive’ neuritic (PHF) change and an accumulation of saccharide. It is probably these latter alterations that mark the process of neuronal (neurofibrillary) degeneration that leads to functional deficits.

Supported in part by the North Western Regional Health Authority