Age-related loss of synaptophysin immunoreactive presynaptic boutons within the hippocampus of APP751SL/PS1M146L and APP751SL/PS1M146L transgenic mice

Neuron and synapse loss are important features of the neuropathology of Alzheimer's disease (AD). Recently, we observed substantial age-related hippocampal neuron loss in APP751(SL)/PS1(M146L) transgenic mice but not in PS1(M146L) mice. Here, we investigated APP751(SL) Mice, PS1(M146L) mice, and APP751(SL)/PS1(M146L) mice for age-related alterations in synaptic integrity within hippocampal stratum moleculare of the dentate gyrus; (SM), stratum lucidum of area CA3 (SL), and stratum radiatum of area CA1-2 (SR) by analyzing densities and numbers of synaptophysimmunoreactive presynaptic boutons (SIPBs). Wildtype mice, APP751(SL) mice and PS1(M146L) mice showed similar amounts of age-related SIPB loss within SM, and no SIPB loss within SL. Both APP751SL Mice and PS1(M146L) mice showed age-related SIPB loss within SR. Importantly, APP751(SL)/PS1(M146L) mice displayed the severest age-related SIPB loss within SM, SL, and SR, even in regions free of extracelhilar A beta deposits. Together, these mouse models offer a unique framework to study the impact of several molecular and cellular events caused by mutant APP and/or mutant PS1 on age-related alterations in synaptic integrity. The observation of age-related SIPB loss within SR of PS1(M146L) mice supports a role of mutant PSI in neurodegeneration. apart from its contribution to alterations in A beta generation.