6533b7cefe1ef96bd1256e90

RESEARCH PRODUCT

P3‐039: Axonal neuritic pathology induces early presynaptic alterations in ps1/APP Alzheimer's mice hippocampus

subject

description

Loss of neurons in the hippocampus correlates with memory impairment in AD. Significant early reduction in the numerical density of hippocampal SOM interneurons was found in single (APPswe) and double (APPswe/ PS1dE9 and APPswe/TauP301S-G272V) transgenic models based on APP over expression and amyloid production. However, this inhibitory population was unaffected in age-matched single PS1 and tau transgenic mice as well as nontransgenic controls. Whereas SOM neuron loss in APPswe/PS1dE9 was associated to the onset of extracellular amyloid pathology in double APP/ tau mice this loss preceded plaque formation. Conclusions: As in human AD, somatostatin cell loss is a common early pathological feature in the hippocampus of different single and double transgenic mice strains harboring APP mutations. Amyloid plaques alone do not account for this selective neuronal degeneration and most likely soluble oligomeric amyloid peptides are the primary causative agent. Finally, the vulnerability of these interneurons may have substantial functional repercussions on local inhibitory processes and memory function in the hippocampus.