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. 1998 Apr 15;18(8):2801-7.
doi: 10.1523/JNEUROSCI.18-08-02801.1998.

Ectopic cell cycle proteins predict the sites of neuronal cell death in Alzheimer's disease brain (VSports注册入口)

J Busser  1 , D S Geldmacher, K Herrup
Affiliations

Ectopic cell cycle proteins predict the sites of neuronal cell death in Alzheimer's disease brain

V体育ios版 - J Busser et al. J Neurosci. .

Abstract

Alzheimer's disease (AD) is a major dementing illness characterized by regional concentrations of senile plaques, neurofibrillary tangles, and extensive neuronal cell death. Although cell and synaptic loss is most directly linked to the severity of symptoms, the mechanisms leading to the neuronal death remain unclear. Based on evidence linking neuronal death during development to unexpected reappearance of cell cycle events, we investigated the brains of 12 neuropathologically verified cases of Alzheimer's disease and eight age-matched, disease-free controls for the presence of cell cycle proteins. Aberrant expression of cyclin D, cdk4, proliferating cell nuclear antigen, and cyclin B1 were identified in the hippocampus, subiculum, locus coeruleus, and dorsal raphe nuclei, but not inferotemporal cortex or cerebellum of AD cases. With only one exception, control subjects showed no significant expression of cell cycle markers in any of the six regions. We propose that disregulation of various components of the cell cycle is a significant contributor to regionally specific neuronal death in AD. VSports手机版.

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Figures

Fig. 1.
Fig. 1.
Top. AD hippocampus stained for cell cycle markers PCNA (A), cyclin B1 (B), cyclin D (C), and cdk4 (D). E, Similar field in a nondemented, age-matched control brain stained for PCNA. The small arrowsindicate cells positive for the respective cell cycle marker. InD, the larger arrow points to a TG3-positive neuron that is cdk4-negative. Scale bars: 50 μm; C, inset, 20 μm.
Fig. 3.
Fig. 3.
Camera lucida drawing of the hippocampus from two AD cases. A, Case 92-447. The trianglesshow the location of cells that were positive for PCNA staining in three sections (combined on the outline of one). Likewise, thesquares show the results of staining for cyclin B1 from three sections, and the open circles show staining from five sections for cyclin D. B, Case 93-221. The symbols are the same with each, representing positive cells in three sections. This case was also stained for cdk4, represented by filled circles. The arrows point to the locations of the representative cells shown in Figure 1. In each figure, the variousCA fields are labeled as indicated. DG, Dentate gyrus. Scale bar, 50 μm.
Fig. 4.
Fig. 4.
Top. AD locus coeruleus stained for cell cycle markers PCNA (A), cyclin B1 (B), cyclin D (C), and cdk4 (D). E, Representative field from a normal brain showing the greater number of cells as well as the lack of staining for PCNA. The arrows indicate cells positive for the respective cell cycle marker. All antigens, except cyclin B1, were revealed using the DAB reaction product (see Materials and Methods).B, The cyclin B1 antigen was revealed using the Vector Red reaction product (see above). C, The asteriskpoints to a labeled non-neuronal cell, most likely a microglial cell. Scale bars: A, B, D, E, 50 μm; C, D, inset, 20 μm.
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