Foundation for Neurologic Diseases
As to date we have contributed $235,115 to the Foundation for Neurologic Diseases. They thank you all for your
continued generous contributions.
Dr. Cindy Lemere
The main focus of our lab is to find a way to prevent or treat Alzheimer's disease (AD). Currently, we are working on a vaccine against beta-amyloid (Ab) protein, the major component of extracellular plaques found in AD brains. We, and others have shown that such a vaccine is very effecting in reducing cerebral plaque burden and improving cognition, especially if given prior to or early in the disease pathogenesis in AD transgenic mouse models. Unfortunately, a Phase IIa clinical trial in humans conducted by ELAN/Wyeth resulted in meningoencephalitis, or brain inflammation, in 18 of 300 (~6%) AD patients. The trial was stopped prematurely. Since then, we have been trying to figure out a way to model this adverse reaction in mice and to develop a newer, safer vaccine. Although no one knows for sure what caused the encephalitis in the human subjects, it is thought that the immune system in some individuals may have recognized the immunizing peptide, synthetic full-length human beta-amyloid, as a self-protein and developed an autoimmune response. Recently, we have developed newer, second-generation beta-amyloid immunizing peptides that include multiple small fragments of beta-amyloid. By doing this, we hope to target the beta-amyloid B cell epitope to stimulate antibody production while avoiding the T cell epitope in hopes of avoiding a cellular immune response to beta-amyloid or its precursor protein. We currently house and use J20 APP tg mice (breeders given to us by Dr. Leonardt Mucke of the Gladstone Institute in San Francisco, CA) and 3xAD-tg mice (breeders kindly provided by Dr. Frank LaFerla of UCI, Irvine, CA). The first model, bearing a transgene for human mutant APP, the amyloid precursor protein, develops Ab plaques, gliosis, neuritic dystrophy, synaptic loss, and cognitive changes with age. The second model, bearing 3 human transgenes for mutant APP, tau, and presenilin1, and develops intraneuronal Ab followed by extracellular beta-amyloid deposition, gliosis, neuritic dystrophy, tau phosphorylation, neurofibrillary tangle formation, and cognitive decline.
Last year, we published a study showing successful lowering of cerebral beta-amyloid levels in a non-human primate, the Caribbean vervet. These animals were brought to St. Kitts from Africa in the late 1600's and mimic humans in depositing Ab plaques in the brain with aging. We are now continuing these studies while further characterizing aging in terms of neuropathology, biochemistry, biomarkers, and cognitive changes in a larger cohort of animals.
In addition, we are interested in the role of complement proteins in the clearance of Ab, particularly as related to antibody-mediated clearance of Ab through immunotherapy. To this end, we have generated a new mouse model, APP tg mice (J20) crossed with C3-null mice. We are now collecting tissues on these mice at multiple ages and in the presence or absence of Abvaccination. Thus far, the mice are viable and survive into adulthood. Much of this work has been carried out by a postdoctoral research fellow, Marcel Maier.
Tim Seabrook, an Instructor in the lab, in addition to working on Ab immunotherapy, has branched out in a new direction to examine the role of microglia in Ab deposition and clearance. He is currently using minocycline to suppress microglial activity in APP tg mice.
Ying Peng, a postdoc who joined the lab last fall, has been busy working on the effects of Chinese herbal extracts on neuronal damage and inflammation caused by beta-amyloid. In addition to her vitro studies of Huperzine A, a supplement now used in China to protect against cognitive decline in AD, she is continuing her thesis work by testing the protective effects of an anti-stroke, anti-oxidant compound in triple transgenic (3xAD-Tg) mice.
Liying Jiang, our lab manager, is currently in charge of our large animal colonies and performs many of our immunotherapy studies from treatment to tissue collection to data analysis.
Thank You note from the Foundation for Neurologic Diseases….
With sincere gratitude, we acknowledge the contribution of $6,000 from the members of the Directory Alumni Council, representing their highly successful fund raising efforts during 2012. This wonderfully generous donation will allow Dr. Cindy Lemere and her team to make new inroads into understanding Alzheimer’s disease.
We thoroughly enjoyed attending DAC’s annual holiday luncheon last December, and we appreciated the chance to meet so many kind and generous-spirited individuals who had worked hard during the year at numerous fund-raising events. Every dollar raised will make a difference at Dr. Lemere’s laboratory and will bring us closer to safe and effective treatment for Alzheimer’s
We look forward to seeing all of you again in December. In the meantime, please do convey our heartfelt thanks to everyone at the DAC for their ongoing interest in and support of our scientific fight against Alzheimer’s disease.
Karen Hodge, Executive Director
Wendy Thaxter, Associate Director
Letter of Thanks 2004
Following is a copy of the Foundations October 25, 2004 letter to the Directory Alumni Council.
Please Accept our heartfelt thanks for the generous gift of $12,500 from the Verizon Alumni Council and congratulations on another successful fund-raising effort! Dr. Lemere joins me in thanking all of those who participated and gave so generously. At the Foundation for Neurologic Diseases, we continue to be impressed by the Counsil's enthusiasm to support our research efforts to eradicate Alzheimer's disease.
Thank you also for the invitation to join you at the Holiday Luncheon. As always, Dr. Lemere and i enjoyed ourselves. We hope that everyone found Dr. Lemere's description of the Foundation's current research into AD interesting and informative.
As Dr. Lemere's dedicated research team continues to unravel the mysteries underlying Alzheimer's, we are sincerely grateful to you and the Council for your support.