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The Neurology Research Laboratory, directed by David Loeffler, D.V.M., Ph.D., and has been located in Beaumont’s Research Institute at Beaumont Hospital – Royal Oak since 2000. The goal of the laboratory is to improve the early diagnosis and treatment of Alzheimer’s and Parkinson’s diseases.
The laboratory's studies focus on discovery of serum and CSF “trait or state” biomarkers for these disorders, and the effects of antibodies on proteins including Aβ, tau, and α-synuclein that feature prominently in the pathological findings of the disorders.
Funding has included support from the National Institutes of Health, the Michael J. Fox Foundation for Parkinson's Research, the Alzheimer's Association, Parkinson's and Movement Disorder Foundation, Oakland University-Beaumont Multidisciplinary Research Grants and private donations.
Intravenous immunoglobulin (IVIG) products are made from plasma antibodies from large numbers of healthy individuals. IVIG’s effects in patients with Alzheimer’s disease were recently evaluated by pharmaceutical manufacturers in several clinical trials. One trial suggested slowing of disease progression in patients with moderate Alzheimer’s, a second found no benefit, and the third is ongoing. A trial examining IVIG’s effects in individuals with mild cognitive impairment (MCI), which may be Alzheimer’s earliest clinical stage, found decreased brain shrinkage after one year.
The main pathological findings in the Alzheimer’s disease brain are senile plaques and neurofibrillary tangles. The Neurology Research Laboratory reported that IVIG contains specific antibodies to amyloid-beta protein (Aβ), the main protein in plaques,1-5 and to tau protein, the main protein in tangles.6-7
The laboratory also found that IVIG contains “Aβ anti-idiotypic” antibodies.8 These are antibodies which are made against anti-Aβ antibodies. The significance of these antibodies is unknown; they could potentially reduce the neuroprotective effects of IVIG’s antibodies to Aβ.
The laboratory recently demonstrated that antibodies to tau protein can reduce its aggregation9 and, infrequently, its phosphorylation.10 Aggregation of tau, when paired with its phosphorylation, is necessary in order to induce neurofibrillary tangle formation from “normal” tau. These results support previous studies in experimental animals (performed elsewhere) suggesting that anti-tau antibodies may be useful to prevent or reduce tangle formation in Alzheimer’s disease and other tauopathies such as frontotemporal dementia and parkinsonism linked to chromosome 17 (FTDP-17) and progressive supranuclear palsy (PSP).
Parkinson’s disease is caused by extensive loss of brain neurons which use dopamine as their neurotransmitter (the chemical which allows neurons to communicate with each other). A protein called α-synuclein is involved with the loss of these neurons. It is found in a structure known as a Lewy body in some surviving dopamine neurons in Parkinson’s and some other disorders. The Neurology Research Laboratory reported that IVIG products contain specific antibodies to α-synuclein,11 and that these antibodies were able to partially protect dopamine neurons in culture from α-synuclein’s neurotoxic effects.12
In another α-synuclein study, the laboratory found no differences between the levels of α-synuclein and antibodies to it between serum samples from individuals with Parkinson's disease, atypical parkinsonian syndromes, rapid eye movement sleep behavior disorder, and healthy controls.13
The laboratory recently measured two proteins, nrf2 and HSPA8, in cerebrospinal fluid samples from Parkinson’s disease patients and aged control subjects, to see if either protein might offer a biomarker to assist in diagnosis of Parkinson’s. The levels of nrf2 were strongly correlated with Parkinson’s-related motor impairments in a subset of Parkinson’s patients. These results were presented at the Movement Disorders Society meeting in June, 2015.
David Loeffler, Ph.D., D.V.M.Director, Neurology Research Laboratory, Beaumont Research InstituteBeaumont Hospital –Royal Oak, Suite 5043811 W. Thirteen Mile Rd.Royal Oak, MI firstname.lastname@example.org
Support Alzheimer’s and Parkinson’s Disease Research
If you would like to make a gift to support the Neurology Research Laboratory at Beaumont, call 248 551-5330 or make a gift online.