Alzheimer neuropathology in non-Down's syndrome mentally retarded adults

Summary We examined the brains of 385 mentally retarded adults aged 23–90 years without Down's syndrome (DS), metabolic disorder, or hydrocephalus to extend our knowledge about the occurrence of Alzheimer-type neuropathology in this population. Relevant measures of neuropathology also were related to selected information available from clinical records. The presence of one or more neurofibrillary tangles (NFT) and/or neuritic plaques (NP) was observed in 63.4% of all cases and varied with age. The prevalence of positive cases was higher when mental retardation was due to head trauma, congenital malformation, or familial factors and when a history of seizures was reported. Comprehensive morphometric analyses of neocortical, hippocampal and parahippocampal areas indicated that recommended agespecific quantitative criteria for the diagnosis of Alzheimer disease [Khachaturian ZS (1985) Arch Neurol 42:1097–1105] were met in 9.5% of cases less than 50 years of age, 54.2% between 50 and 65, 70% between 66 and 75, and 87% of the cases greater than 75 years of age. However, a limited immunohistochemical study revealed that in most cases the NP did not have a neuritic component containing paired helical filaments and in this respect most of the plaques observed in this population may differ from those most strongly associated with Alzheimer disease. In addition, substantial numbers of NFT were seen in frontal cortex, contrasting with results reported in the literature for nonretarded populations. The number of NP per mm² consistently increased with age for all areas examined, while the relationship between NFT density and age varied across areas, and was clearly not monotonic. Our studies show that the neuropathological lesions currently considered hallmarks of Alzheimer disease are prevalent among non-DS mentally retarded adults, and the regional density of these lesions is high. Thus, while people with DS are affected at an earlier age, clear Alzheimer neuropathology develops in many mentally retarded individuals.Supported in part by funds from the New York State Office of Mental Retardation and Developmental Disabilitics, as well as by Grant No. PO1 HD 22634, awarded to H. Wisniewski by the National Institutes of Health. Maria Barcikowska is a Visiting Scientist from the Department of Neurology, Medical Academy of Warsaw, Poland and Christian Bancher is a Visiting Scientist from the Neurological Institute, University of Vienna, Austria