Fig. 1

Early-stage neuronal loss precedes hippocampal neuronal compensation at 12 months, before robust decline. To assess neuronal loss in TgF344-AD rats, entorhinal cortical (EC) and hippocampal neurons were quantified by NeuN⁺ staining in NTg and TgF344-AD rats at 9, 12 and 15 months of age (n = 8–9 rats/genotype/age). a Representative NeuN⁺ staining in 9-month-old NTg and Tg rats demonstrates a loss of EC layer II neurons in TgF344-AD rats (red outline). b In the hippocampus, NeuN staining at 15 months demonstrates thinning of pyramidal and granular cell layers in Tg rats. c No significant genotype differences were detected at any age in the total EC neurons. d Tg rats exhibited a significant overall deficit (P = 0.03) in layer II EC neurons. e, f There were significant age × genotype interactive effects (both P = 0.02) on the total hippocampal neurons and the CA1 pyramidal layer (PL) neurons. The Tg rats exhibited an overall significant loss of g CA3 PL neurons (P = 0.02) and h DG granular cell layer (GCL) neurons (P = 0.0002), notably at 9 and 15 months. Scale bars, 200 μm (a) and 400 μm (b). Data are mean ± SEM; two-way ANOVA with correction for multiple comparisons with a Holm-Sidak post hoc test (see Table 1 for complete statistics); *P < 0.05, **P < 0.01