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
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
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
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.
- Int Immunopharmacol 2010; 10:115-119.
- J Neurosci Methods 2010; 187:263-269.
- J Neurosci Methods 2011; 195:249-254.
- Immunol Letters 2013; 154:7-11.
- Analytical Biochem 2015;481:43-54.
- Int Immunopharmacol 2013; 16:424-428.
- Int Immunopharmacol 2014; 21:279-282.
- Autoimmunity 2015;48:196-200.
- Biochemistry 2015; 54:293-302.
- Exp Gerontology 2015; 67:15-18.
- Clin Exp Immunol 2010; 161: 527-535.
- Int Immunopharmacol 2012; 14:550-557.
- PLoS ONE 2012; 7: e52285.