Neurology Research

Department Overview

Beaumont Research Institute's Neurology Research Laboratory, directed by David Loeffler, D.V.M., Ph.D., moved to Beaumont Hospital, Royal Oak, MI in 2000 from Sinai Hospital of Metropolitan Detroit where it was started in 1990. The long-term goal of the laboratory's research is to improve the diagnosis and treatment of Alzheimer's and Parkinson's diseases. The laboratory's studies focus on the significance of brain immune and inflammatory processes in the development and progression of these disorders.

The laboratory's studies have been supported by the National Institutes of Health, the Michael J. Fox Foundation for Parkinson's Research, the Alzheimer's Association, and other private foundations. The laboratory recently received funding from Oakland University-Beaumont Multidisciplinary Research Grants and the Parkinson's and Movement Disorder Foundation, as well as generous donations from Mr. and Mrs. Frederick Erb and family, Mr. Norman Merollis, and Mrs. Martha Loeffler to support its research efforts. These funds have permitted the laboratory to pursue new directions.

Foremost in these studies is the investigation of Intravenous Immunoglobulin (IvIg), a commercial drug composed of pooled antibodies from thousands of healthy donors. IvIg treatment has resulted in improvement in cognitive scores in two clinical trials (performed elsewhere) with Alzheimer's patients; the laboratory's IvIg-related studies are focused on characterizing the antibodies in this drug which may be responsible for its benefits in Alzheimer's patients, as well as those which may be useful to treat individuals with Parkinson's disease and related disorders. The laboratory is collaborating in these studies with John Finke, Ph.D., and Xiangqun Zeng, Ph.D., from Oakland University's Department of Chemistry.

Key Research Areas

Alzheimer's Disease

A key pathological finding in the Alzheimer's brain is senile plaques, whose major protein is amyloid-beta (Aβ). The laboratory recently published its findings (International Immunopharmacology 2010;10:115-119) in which antibodies to Aβ were compared between different IvIg preparations; antibodies to the most neurotoxic form of Aβ, termed Aβ soluble oligomers, were present in IvIg, and surprisingly, there were significant differences between different IvIg preparations in their levels of these antibodies. A related paper highlighted the difficulties posed by nonspecific antibody binding when these antibodies are measured by immunoassay (Journal of Neuroscience Methods 2010;187:263-9), and a recently accepted paper examined the specificity of the procedure most commonly used to measure Aβ soluble oligomers (Journal of Neuroscience Methods 2010, in press). A fourth manuscript investigated the effects of external beam radiation (radiation therapy) on Aβ fibrils, which is the conformation of Aβ present in senile plaques (Radiation Research 2011, in press). Studies are continuing to compare serum anti-Aβ antibodies from individuals with Alzheimer's disease, subjects with mild cognitive impairment, and aged normal individuals. Proteomics studies to look for combinations of plasma or urinary proteins which may serve as "biomarkers" for early detection of Alzheimer's are also planned for the coming year.

Parkinson's Disease

The main pathological finding in Parkinson's disease is extensive loss of dopaminergic neurons in an area of the brain called the substantia nigra. A protein called alpha-synuclein (α-synuclein) has been implicated in the loss of these neurons; it is found in a structure known as a Lewy body in some of the surviving Parkinson's dopamine neurons. Our laboratory recently published results showing that IvIg products contain specific antibodies to different conformations of α-synuclein (Clinical and Experimental Immunology 2010;161:527-35). Studies in the coming year will examine the protective ability of IvIg against the neurotoxic effects of α-synuclein on cultured dopamine neurons, as well as IvIg's effects on the development of different conformations of α-synuclein.

Active Research

One of the laboratory's ongoing projects is to evaluate the development of Alzheimer's-type pathology in a mouse model of insulin resistance. The study is conducted in collaboration with investigators from the University of Toledo. Another long-term study is measuring pathological proteins and the antibodies to these proteins in serum samples from patients with Alzheimer's disease, mild cognitive impairment and aged normal controls. This work is in collaboration with investigators at the Rush University Medical Center in Chicago. A project that has recently begun compares two methodologies, enzyme-linked immunosorbent assay (ELISA) and piezoimmunosensor technology, for measurement of Alzheimer's-related serum antibodies. The Parkinson's disease-related studies are measuring the levels of antibodies to key Parkinson's pathological proteins in IvIg preparations.

Department Highlights

Recent publications from the Neurology Research Laboratory include the following:

  • Loeffler DA.Significance of complement activation in Alzheimer's disease.US Neurology 2008; 4:52-55.
  • Camp DM, Loeffler DA, Farrah DM, LeWitt PA.Cellular immune response to intrastriatally implanted allogeneic bone marrow stromal cells in a rat model of Parkinson's disease.Journal of Neuroinflammation 2009, 6:17.
  • Klaver AC, Finke JM, Digambaranath J, Balasubramaniam M, Loeffler DA.Antibody levels to Aβ1-42 conformations differ between intravenous immunoglobulins.International Immunopharmacology 2010; 10:115-119.
  • Klaver AC, Patrias LM, Coffey MP, Finke JM, Loeffler DA.Measurement of anti-Abeta1-42 antibodies in intravenous immunoglobulin with indirect ELISA: the problem of nonspecific binding.Journal of Neuroscience Methods 2010;187:263-9.
  • Patrias LM, Klaver AC, Coffey MP, Loeffler DA.Specific antibodies to soluble alpha-synuclein conformations in intravenous immunoglobulin preparations.Clinical and Experimental Immunology 2010; 161:527-35.
  • Klaver AC, Patrias LM, Finke JM, Loeffler DA.Specificity and sensitivity of the Abeta oligomer ELISA.J Neuroscience Methods, 2010 Dec 14. [Epub ahead of print]
  • Patrias, LM, Klaver AC, Coffey MP, Finke JM, Digambaranath JL, Dang L, Martinez AA, Loeffler DA.Effects of external beam radiation on in vitro formation of Abeta1-42 fibrils and preformed fibrils.Radiation Research, 2011 Jan 4 [Epub ahead of print]
  • At the Society for Neuroscience annual meeting in San Diego in November 2010, the laboratory presented three posters describing its research

Contact Information

Principal Investigator

Title

Email

Research of Interest

David A. Loeffler, D.V.M., Ph.D.

Director, Neurology Research Laboratory

DLoeffler@beaumont.edu

Inflammatory processes, complement activation, neuroimmunology/neuroinflammation