Progressive degeneration of nonphosphorylated neurofilament protein-enriched pyramidal neurons predicts cognitive impairment in Alzheimer's disease:: Stereologic analysis of prefrontal cortex area 9

被引:144
作者
Bussière, T
Giannakopoulos, P
Bouras, C
Perl, DP
Morrison, JH
Hof, PR
机构
[1] CUNY Mt Sinai Sch Med, Kastor Neurobiol Aging Labs, New York, NY 10029 USA
[2] CUNY Mt Sinai Sch Med, Fishberg Res Ctr Neurobiol, New York, NY 10029 USA
[3] CUNY Mt Sinai Sch Med, Dept Geriatr & Adult Dev, New York, NY 10029 USA
[4] CUNY Mt Sinai Sch Med, Dept Ophthalmol, New York, NY 10029 USA
[5] CUNY Mt Sinai Sch Med, Dept Pathol Neuropathol, New York, NY 10029 USA
[6] CUNY Mt Sinai Sch Med, Dept Psychiat, New York, NY 10029 USA
[7] Elan Pharmaceut Inc, San Francisco, CA 94080 USA
[8] Univ Geneva, Sch Med, HUG Belle Idee, Dept Psychiat,Clin Geriatr Psychiat, CH-1225 Geneva, Switzerland
[9] Univ Geneva, Sch Med, HUG Belle Idee, Dept Psychiat,Div Neuropsychiat, CH-1225 Geneva, Switzerland
[10] Univ Lausanne, Sch Med, Dept Psychogeriatr, CH-1008 Prilly, Switzerland
关键词
brain aging; dementia; neocortex; neurofilament protein; pyramidal neuron; stereology; tangle;
D O I
10.1002/cne.10760
中图分类号
Q189 [神经科学];
学科分类号
071006 ;
摘要
We performed a stereologic analysis of a subset of pyramidal neurons known to be vulnerable in Alzheimer's disease (AD) and characterized by particularly high somatodendritic levels of nonphosphorylated neurofilament protein. In the neocortex, these large pyramidal neurons reside in the deep part of layer III (layer IIIc) and the superficial part of layer V (layer Va). We focused on prefrontal cortex area 9 in elderly control cases in comparison to cases with different degrees of cognitive dysfunction. The results confirmed that these neurons are preferentially vulnerable in AD, as their numbers decrease dramatically in cases with definite dementia, correlating strongly with the severity of the disease, to a nearly complete loss (>90%) in the endstages of AD. Furthermore, a triple-labeling experimental paradigm revealed that these particular neurons are far more likely to develop neurofibrillary tangles (NFT) and do so at a faster rate than other pyramidal cells. Nonphosphorylated neurofilament protein-rich neurons also shrink considerably during formation of NFT and the largest among them are preferentially affected. Laminar differences in the severity of these effects were observed, layer Va being more severely affected, possibly correlating with the involvement of specific cortical projections. These data reveal that different populations of neurons prone to NFT formation are lost at different rates in AD, and that nonphosphorylated neurofilament protein-enriched neurons emerge as a strikingly vulnerable subpopulation. of neurons. Their preferential involvement suggests that neurons providing specific corticocortical connections between association areas are at high risk for degeneration in AD.
引用
收藏
页码:281 / 302
页数:22
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