wing primary antibodies were used: 1) to probe astrocytes and microglial cells: rabbit polyclonals anti-S100 , anti-GFAP and anti-Iba1 ; and 2) to probe hyperphosphorylated and misfolded tau: mouse monoclonals AT8 , Alz50, CP13, MC1 21 / 26 Characterizing a Model of -Amyloid Toxicity , PG5, PHF-1 and TG-3 . Immunoreactivities were visualized using diaminobenzidine chromagen. The sections were then counterstained in 1% Congo red aqueous solution for 1 hr at room temperature to visualize dense-core plaques. Finally, hematoxylin and eosin staining was used to provide cytological detail. Axonal pathology. To study dense-core plaques PubMed ID:http://www.ncbi.nlm.nih.gov/pubmed/19784385 and axonal pathology, FFPE hemispheres from three 24-month-old rTg9191 mice and two non-transgenic littermates were sectioned at 16 m in the parasagittal plane. To visualize axon structure, every 15th section was rehydrated; subjected to antigen retrieval; blocked; then incubated with monoclonal antibody SMI-312, directed against axonal neurofilaments Background Sniper blocking reagent, 4C, overnight) followed by Alexa Fluor 555-conjugated donkey-anti-mouse blocking reagent). To reveal dense-core plaques, sections immunostained with SMI-312 were counterstained with freshly order BKM 120 prepared 1% thioflavin-S aqueous solution at room temperature for 5 min followed by differentiation using 70% ethanol. For all immunostaining, sections were also exposed to secondary antibodies only. In such cases, no positive labeling was observed. Hematoxylin and eosin stain. To visualize brain structure, eight APP/TTA, two TTA, two APP and two non-Tg mice were analyzed. Three 5 m-thick sections from each animal, at ~0.84, 1.20, and 1.56 mm lateral from midline, were prepared. Hematoxylin and eosin staining was performed on selected sections according to standard protocols. Statistics Statistics were performed using StatView Version 5.0.1. Data are expressed as mean SEM. ~~ Neoplastic transformation of human fibroblasts and epithelial cells is thought to result from the sequential acquisition of genetic and/or epigenetic alterations in specific genes. Much progress has been made in identifying and characterizing the genetic elements required to transform normal human cells. Collectively, the results of these studies suggest that the transformation of human cells in vitro depends upon functional alterations in four to six 
genes. These alterations include changes in genes involved in telomere maintenance, disruption of tumor suppressor pathways, and activation of oncogenes. For example, the transformation of normal human fibroblasts requires the co-expression of MYC, RAS, and hTERT together with the functional PubMed ID:http://www.ncbi.nlm.nih.gov/pubmed/19783938 loss of the RB, PTEN, and p53 tumor suppressor pathways. However, a review by Duesberg and colleagues suggests that aneuploidy, in which a cell contains an abnormal number of chromosomes, is the primary cause of, and driving force behind, tumorigenesis: they state that aneuploidy results in an imbalance of gene expression, leading to the initiating event that initiates the transformation of normal cells. An alternative explanation for the role of aneuploidy in tumorigenesis comes from mouse models harboring modifications in mitotic checkpoint genes. Studies of these mice have indicated that those showing reduced expression of mitotic checkpoint components, such as Bub1, BubR1, CENP-E, and Mad2, display an increased aneuploidy. In some mice,, reduced levels of CENP-E are associated with an increase in spontaneous tumorigenesis. However, m