Abstract
It is widely accepted that Aβ plays a pivotal role in the pathogenesis of Alzheimer's disease (AD) [27]. Attention has been focused mainly on how extracellular Aβ exerts its effects on neuronal cells [7,11,16,32]. However, neuronal degeneration from an accumulation of intracellular Aβx-42 (iAβ42) occurs in presenilin 1 (PS1) mutant mice without extracellular Aβ deposits [5]. In the present study, intracellular deposits of iAβ42 are correlated with apoptotic cell death in AD and PS-1 familial AD (PS1 FAD) brains by means of triple staining with antibodies to Aβ, TUNEL, and staining with Hoechst 33342. Neurons simultaneously positive for iAβ42 and the TUNEL assay were significantly more abundant in AD brains than in controls. The number of apoptotic neurons with intracellular neurofibrillary tangles (iNFTs) was insignificant. Our results indicate that intraneuronal deposition of a neurotoxic form of Aβseems to be an early event in the neurodegeneration of AD.