Tara L. Spires-Jones, DPhil

  • Lab Phone: 617-726-1263

Research Investigator Profile

Tara Spires-Jones, DPhil

Tara L. Spires-Jones, DPhil

  • Assistant Professor of Neurology,
    Harvard Medical School
  • Assistant in Neuroscience
    Massachusetts General Hospital

 

 

Research Description

My research focuses on questions of mechanisms and reversibility of neuronal degeneration in Alzheimer’s disease.  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 advanced imaging techniques, mouse models, and human tissue, we 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.  We are 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.

Research interests Neurodegeneration and plasticity in disease and aging
Research techniques Multiphoton imaging, array tomography, viral-mediated gene transfer
Diseases studied Alzheimer’s disease, Frontotemporal Dementia, and Aging
Selected publications
  1. Koffie RM, Hashimoto T, Tai H-C, Kay KR, Serrano-Pozo A, Joyner D, Hou S, Kopeikina KJ, Frosch MP, Lee VM, Holtzman DM, Hyman BT, Spires-Jones TL. Apolipoprotein E4 effects in Alzheimer disease are mediated by synaptotoxicoligomeric amyloid-beta. Brain: 2012; 135:2155.
  2. de Calignon A, Polydoro M, Suárez-Calvert M, William C, Adamowicz DH, Kopeikina KJ, Pitstick R, Sahara N, Ashe KH, Carlson GA, Spires-Jones TL, Hyman BT.  Propagation of tau pathology in a model of early Alzheimer’s disease.  Neuron 2012; 73:685.
  3. Kopeikina KJ, Carlson GA, Pitstick R, Ludvigson AE, Peters A, Leubke JI, Koffie RM, Frosch MP, Hyman BT, Spires-Jones TL. Tau Accumulation Causes Mitochondrial Distribution Deficits in Neurons in a Mouse Model of Tauopathy and in Human AD Brain. Am J Pathol. 2011; 179:2071.
  4. Koffie RM, Farrar CT, Saidi L-J, William CM, Hyman BT, Spires-Jones TL. Nanoparticles enhance brain delivery of blood-brain-barrier impermeable probes for in vivo optical and magnetic resonance imaging.  PNAS 2011; 108: 18837. (covered in Nature Research Highlights Nature 479:271).
  5. de Calignon A, Fox LM, Pitstick R, Carlson GA, Bacskai B, Spires-Jones TL, Hyman BT. Tangles appear as a consequence of caspase activation.  Nature 2010;  464: 1201-4.
  6. Koffie R, Meyer-Luehmann M, Mielke M, Garcia-Alloza M, Micheva KD, Smith SJ, Lee V, Hyman BT, Spires-Jones TL. Oligomeric amyloid beta interacts with postsynaptic densities and correlates with senile plaque-associated synapse loss. Proc Nat Acad Sciences 2009; 106:4012-4017. PMCID PMC2656196
  7. Meyer-Luehmann M, Spires-Jones TL, Prada C, Garcia-Alloza M, de Calignon A, Rozkalne A, Koenigsknecht-Talboo J, Holtzman DM, Bacskai BJ, Hyman BT: Rapid appearance and local toxicity of amyloid-b plaques in a mouse model of Alzheimer’s disease. Nature 2008; 451:720-724.
NCBI PubMed link

NCBI PubMed Publications, Spires, TL
NCBI PubMed Publications, Spires-Jones, TL

E-mail address tspires@partners.org
Lab mailing address MassGeneral Institute for Neurodegenerative Disease
Building 114, Room
114 16th Street
Charlestown, MA 02129

 

10/19/2012