Robert D. Moir, PhD

Assistant Professor of Neurology

My research focuses on mechanisms and reversibility of neuronal degeneration in Alzheimer’s disease models. During the course of Alzheimer’s disease, neurons lose synapses and specifically dendritic spines, the postsynaptic element of most excitatory synapses in the brain. Neurons also suffer changes in neurite architecture such as curvature caused by senile plaques and axonal and dendritic swellings associated with plaque and tangle pathology.

Using multiphoton imaging, I currently study the effects of accumulation of amyloid beta into senile plaques and phosphorylated tau into neurofibrillary tangles on dendritic spines, neurite morphology, and neuronal death. With tools such as inducible transgenic models, drug administration, and viral transduction to introduce genes of interest into neurons, I am investigating mechanisms underlying these changes and whether treatments such as immunotherapy can reverse some of the damage. Since synapses and neurites are very plastic structures, they have the potential to recover after treatments, giving hope for some functional recovery in patients if we can halt neurodegenerative processes in the future.

Selected Publications

Spires TL, Meyer-Luehmann M, Stern EA, McLean PJ, Skoch J, Nguyen PT, Bacskai BJ, Hyman BT: Dendritic spine abnormalities in amyloid precursor protein transgenic mice demonstrated by gene transfer and intravital multiphoton microscopy. J Neurosci 2005; 25:7278-7287.

SantaCruz K*, Lewis J*, Spires T*, Paulson J, Kotilinek L, Ingelsson M, Guimaraes A, Deture M, Ramsden M, McGowan E, Forster C, Orne J, Mariash A, Kuskowski M, Hyman B, Hutton M, Ashe KH. Recovery of memory after neuron loss and brain atrophy in a mouse model of tauopathy. Science 2005; 309:476-481.

Spires TL, Orne JD, SantaCruz K, Pitstick R, Carlson GA, Ashe KH, Hyman BT: Region-specific dissociation of neuronal loss and neurofibrillary pathology in a mouse model of tauopathy. Am J Pathol 2006; 168:1598-1607.

Fulga TA, Elson-Schwab I, Khurana V, Steinhilb ML, Spires TL, Hyman BT, Feany MB: Abnormal bundling and accumulation of F-actin mediates tau-induced neuronal degeneration in vivo. Nature Cell Biology 2006; Epub ahead of print.