In VivoOlfactory Model of APP-Induced Neurodegeneration Reveals a Reversible Cell-Autonomous Function

• DOI: 10.1523/jneurosci.1714-11.2011
• Publication Date: 2011-09-28T20:25:18Z
• Authors: Ning Cheng; Huaibin Cai; Leonardo Belluscio
• Keywords: Male; Mice, 129 Strain; Sensory Receptor Cells; Cell Differentiation; Mice, Transgenic; Mice, Inbred C57BL; Smell; Amyloid beta-Protein Precursor; Disease Models, Animal; Mice; 03 medical and health sciences; 0302 clinical medicine; Animals, Newborn; Nerve Degeneration; Animals; Humans; Female; Microscopy, Immunoelectron

Amyloid precursor protein (APP) has long been linked to the neurodegeneration of Alzheimer's disease (AD), but associated cell death difficult capture in vivo , and role APP effecting neuron loss is still unclear. Olfactory dysfunction an early symptom AD with amyloid pathology olfactory epithelium correlating well brain patients. As sensory neurons (OSNs) regenerate continuously immature mature OSNs coexisting same epithelium, we sought use this unique system study APP-induced neurodegeneration. Here have developed olfactory-based transgenic mouse model that overexpresses humanized containing familial mutations (hAPP) either or OSNs, found despite absence extracellular plaques a striking number apoptotic were detected by 3 weeks age. Importantly, apoptosis was restricted specific population overexpressing hAPP, sparing those without hAPP. Interestingly, observed widespread could be rapidly rescued reducing hAPP expression levels neurons. Together, these data argue alone induce cell-autonomous both neurons, challenging notion are necessary for Furthermore, show hAPP-induced reversible, suggesting AD-related neural potentially rescued. Thus, propose will not only help determine mechanisms underlying also serve as platform test possible treatments.