Brainstem Alzheimer's-like pathology in the triple transgenic mouse model of Alzheimer's disease.

The triple transgenic mouse (3xTgAD), harboring human APP(Swe), PS1(M146V) and Tau(P301L) genes, develops age-dependent forebrain intraneuronal Abeta and tau as well as extraneuronal plaques. We evaluated brainstem AD-like pathology using 6E10, AT8, and Alz50 antibodies and unbiased stereology in young and old 3xTgAD mice. Intraneuronal Abeta occurred in the tectum, periaqueductal gray, substantia nigra, red nucleus, tegmentum and mesencephalic V nucleus at all ages. Abeta-positive neuron numbers significantly decreased in the superior colliculus and substantia nigra while AT8-positive superior colliculus, red nucleus, principal sensory V, vestibular nuclei, and tegmental neurons significantly increased between 2 and 12 months. Alz50-positive neuron numbers increased only in the inferior colliculus between these ages. Dual labeling revealed a few Abeta- and tau-positive neurons. Plaques occurred only in the pons of female 3xTgAD mice starting at 9 months. 3xTgAD mice provide a platform to define in vivo mechanisms of Abeta and tau brainstem pathology.