Perlmutter Lab

Joel S. Perlmutter, MD

The lab focuses on Parkinson disease and related disorders. We investigate mechanisms of action of deep-brain stimulation — a dramatic new treatment. These studies combine PET measures of regional cerebral blood flow, cognitive testing and quantified measures of movement. These studies have led to new insights into the mechanisms of deep brain stimulation as well as offer an opportunity for functional mapping of basal ganglia function in humans.

We have an ongoing investigation of dementia in people with Parkinson disease. This study includes cognitive, clinical, genetic and neuroimaging-based measures (PET and MRI) with subsequent comparison to post-mortem findings.

We also test new drugs that might rescue injured nigrostriatal neurons (a model of PD). For these, we use PET to measure dopamine pathways and also quantify motor behavior. We are actively developing and validating biomarkers of PD progression using nonhuman primate models. In people with PD, we develop and apply MR and PET methods for objective measures of disease severity. These measures enhance our genetic and etiologic studies of PD (for example investigating the potential of welding exposure or manganese toxicity to lead to nigrostriatal damage).

In other patient-oriented research, we have developed a biorepository linked to clinical phenotype data on a variety of movement disorders to act as a resource for ongoing and future biomarker and genetic studies. One of the new studies is a multicenter collaboration studying focal dystonias. These studies have included the development of a new resource at Washington University called the NeuroClinical Research Unit that has also provided the basis of the Brain, Behavior and Performance Unit of the CTSA at WU. The BBPU supports new patient-oriented research studies in neuropsychiatric disorders.

We also use PET to measure radioligand binding and sensorimotor processing in dystonia. We developed a new animal model of dystonia to investigate pharmacologic and physiologic changes. We use PET to investigate drug-mediated pathways in the brain and parse out the effects of selective dopaminergic agonists.

Finally, we investigate the relationship between blood flow responses in the brain with electrophysiological responses done in the same animals. These animal studies provide insights into the basic mechanisms of many of the studies that we subsequently apply to humans.

Principal investigator

Joel  Perlmutter, MD

Joel Perlmutter, MD

Elliot Stein Family Professor of Neurology
Adult, Movement Disorders
Professor, Radiology, Neuroscience, Physical Therapy and Occupational Therapy

  Perlmutter lab

Top areas of adult care: Parkinson’s disease, Huntington’s disease, Tourette syndrome

Recent publications

  • Structure of alpha-synuclein fibrils derived from human Lewy body dementia tissueDhavale, D. D., Barclay, A. M., Borcik, C. G., Basore, K., Berthold, D. A., Gordon, I. R., Liu, J., Milchberg, M. H., O’Shea, J. Y., Rau, M. J., Smith, Z., Sen, S., Summers, B., Smith, J., Warmuth, O. A., Perrin, R. J., Perlmutter, J. S., Chen, Q., Fitzpatrick, J. A. J. & Schwieters, C. D. & 3 others, Tajkhorshid, E., Rienstra, C. M. & Kotzbauer, P. T., Dec 2024, In: Nature communications. 15, 1, 2750.Research output: Contribution to journal › Article › peer-review
  • Replication and reliability of Parkinson's disease clinical subtypesCash, T. V., Lessov-Schlaggar, C. N., Voegtli, E., Myers, P. S., Jackson, J. J., Maiti, B., Kotzbauer, P. T., Perlmutter, J. S. & Campbell, M., Jul 2024, In: Parkinsonism and Related Disorders. 124, 107016.Research output: Contribution to journal › Article › peer-review
  • Design, synthesis, and biological evaluation of multiple F-18 S1PR1 radiotracers in rodent and nonhuman primateQiu, L., Jiang, H., Zhou, C., Tangadanchu, V. K. R., Wang, J., Huang, T., Gropler, R. J., Perlmutter, J. S., Benzinger, T. L. S. & Tu, Z., Jun 13 2024, In: Organic and Biomolecular Chemistry. 22, 26, p. 5428-5453 26 p.Research output: Contribution to journal › Article › peer-review
  • Time for Clinical Dopamine Transporter Scans in Parkinsonism? Not DAT YetDi Luca, D. G. & Perlmutter, J. S., Jun 11 2024, In: Neurology. 102, 11, p. e209558Research output: Contribution to journal › Editorial
  • PET Quantification of [18F]VAT in Human Brain and Its Test-Retest Reproducibility and Age DependenceO'Donnell, J. L., Soda, A. K., Jiang, H., Norris, S. A., Maiti, B., Karimi, M., Campbell, M. C., Moerlein, S. M., Tu, Z. & Perlmutter, J. S., Jun 3 2024, In: Journal of nuclear medicine : official publication, Society of Nuclear Medicine. 65, 6, p. 956-961 6 p.Research output: Contribution to journal › Article › peer-review