T. Gomezisla et al., PROFOUND LOSS OF LAYER-II ENTORHINAL CORTEX NEURONS OCCURS IN VERY MILD ALZHEIMERS-DISEASE, The Journal of neuroscience, 16(14), 1996, pp. 4491-4500
The entorhinal cortex (EC) plays a crucial role as a gateway connectin
g the neocortex and the hippocampal formation. Layer II of the EC give
s rise to the perforant pathway, the major source of the excitatory in
put to the hippocampus, and layer IV receives a major hippocampal effe
rent projection. The EC is affected severely in Alzheimer disease (AD)
, likely contributing to memory impairment. We applied stereological p
rinciples of neuron counting to determine whether neuronal loss occurs
in the EC in the very early stages of AD. We studied 20 individuals w
ho at death had a Clinical Dementia Rating (CDR) score of 0 (cognitive
ly normal), 0.5 (very mild), 1 (mild), or 3 (severe cognitive impairme
nt). Lamina-specific neuronal counts were carried out on sections repr
esenting the entire EC. In the cognitively normal (CDR = 0) individual
s, there were similar to 650,000 neurons in layer II, 1 million neuron
s in layer IV, and 7 million neurons in the entire EC. The number of n
eurons remained constant between 60 and 90 years of age. The group wit
h the mildest clinically detectable dementia (CDR = 0.5), all of whom
had sufficient neurofibrillary tangles (NFTs) and senile plaques for t
he neuropathological diagnosis of AD, had 32% fewer EC neurons than co
ntrols. Decreases in individual lamina were even more dramatic, with t
he number of neurons in layer II decreasing by 60% and in layer IV by
40% compared with controls. In the severe dementia cases (CDR = 3), th
e number of neurons in layer II decreased by similar to 90%, and the n
umber of neurons in layer IV decreased by similar to 70% compared with
controls. Neuronal number in AD was inversely proportional to NFT for
mation and neuritic plaques, but was not related significantly to diff
use plaques or to total plaques. These results support the conclusion
that a marked decrement of layer II neurons distinguishes even very mi
ld AD from nondemented aging.