R. Sadowski et al., Entorhinal cortex of aged subjects with Down's syndrome shows severe neuronal loss caused by neurofibrillary pathology, ACT NEUROP, 97(2), 1999, pp. 156-164
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.