Entorhinal cortex of aged subjects with Down's syndrome shows severe neuronal loss caused by neurofibrillary pathology

In Alzheimer's disease (AD), neurofibrillary degeneration of neurons starts in the transentorhinal cortex and spreads in a time-dependent manner to th e entorhinal cortex, which provides a major input to the hippocampus - a ke y structure of the memory system. People with Down's syndrome (DS) develop neurofibrillary changes more than 30 years earlier than those with sporadic AD. To characterize AD-related pathology in the entorhinal cortex in DS, w e examined seven subjects with DS of 60-74 years of age who died in the end stage of AD, and four age-matched control subjects. The volume of the ento rhinal cortex in brains of subjects with DS was 42% less than that in contr ol cases; however, the total number of neurons free of neurofibrillary chan ges was reduced in DS by 90%: from 9.619.000 +/- 914,000 (mean +/- standard deviation) to 932,000 +/- 504,000. The presence of 2,488,000 +/- 544,000 n eurofibrillary tangles in the entorhinal cortex of people with DS, the prev alence of endstage tangles, and the significant negative correlation betwee n the total number of intact neurons and the percentage of neurons with neu rofibrillary changes indicate that neurofibrillary degeneration is a major cause of neuronal loss in the entorhinal cortex of people with DS. The rela tively low amyloid load (7 +/- 1%) and lack of correlation between the amyl oid load and the volumetric or neuronal loss suggest that the contribution of beta-amyloid to neuronal loss in the entorhinal cortex is unsubstantial.