Quantitative analysis of neurodegeneration and cell death in Psen cDKO Cx†‡.

†Values for Fluoro-Jade B and TUNEL represent percentage of positive cells based on stereological estimates of total cell number. Note that although Psen1 gene inactivation, measured by Psen1 mRNA levels, occurs by 3–4 weeks, death is not increased at this timepoint. Since Psen1 protein levels persist and gradually diminish between P22 and 6 weeks [14], the delay in onset of death is likely due to the continued presence of Psen1 protein subsequent to gene inactivation.‡All calculations of total % death are based on stereological estimates of cortical cell number at 2 months of age (4.8×106 cells/hemisphere; [10] and at 4 months of age (Fig. 1) combined with an estimate of 5 mm width of one hemisphere. Raw data (# dead cells/20 µm-thick sagittal section) was converted to a % by the following calculations: 1) the fraction of a hemisphere represented by one 20-µm thick section (1 section = 20 µm/5000 µm, or 1/250th of a hemisphere), 2) the average number of cortical cells per 20 µm -thick section (4,800,000 cells/hemisphere (2 mo) or 1,500,000 cells/hemisphere (4 mo) ×1/250th of a hemisphere = 19,200 cells/20 µm section), and 3) the percentage of dying cells per section (average number of dead cells per 20 µm section/19,200 total cells).#actual value = −9.6% (p = 0.09; n = 4 pairs); ND, not determined. *[10]