Whereas a plethora of studies focusses on extracellular plaque deposition, only a very limited amount of reports
deal with intraneuronal accumulation of Aβ peptides in human AD. However, over the past years, accumulating evidence
points to a significant role of intraneuronal Aβ triggering the pathological cascade leading to neurodegeneration in
Alzheimer’s disease (AD). Much of the data originate from studies on transgenic mouse models of AD, where initial
intraneuronal Aβ accumulation which predes extracellular plaque deposition, has been repeatedly reported. The current
review discusses the impact of this finding on the future development of novel mouse models for preclinical research as a
basis for therapeutic intervention.