Screening for antibodies that modulate the risk for Alzheimer’s disease
We screen blood and saliva of elderly (90+) nondemented individuals to identify antibodies that protected them from developing Alzheimer’s disease. The data generated will be used (i) for predicting Alzheimer’s disease risk in individuals (ii) for new Alzheimer’s disease therapeutics, and (iii) to guide the development of a vaccine to pathogen-induced Alzheimer’s disease.
We calibrated the screen assay, obtained regulatory approval and are collecting samples for the full screen. IP will be generated after the screen is complete, and the targets are validated in an independent manner. My lab works on molecular aspects of aging. Originally I come from the field of the nuclear lamina (responsible among others for the premature aging disease Hutchinson-Gilford progeria syndrome) and lifespan regulating pathways, with a strong background in method development (for example see https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5790613/). Reading the P. gingivalis (PG) paper by Dominy et al (2018), I was surprised how prevalent brain infection with PG is (and later seeing similar data for HSV). But then I noticed that the 102 year old (healthy nondemented) control, the oldest person in that set, was the only one completely negative for PG. This made me think an exceptional immune reaction may have helped her keep her brain clear of PG for so long. Going through the literature, I found ample evidence for the involvement of the immune system in Alzheimer’s disease, but no direct testing of the antibody repertoire to pathogens, at least not by modern standards. Commercial Viability People outside the field, or within the field and “committed” to a paradigm, are surprised by the involvement of pathogens and the strength of the evidence to support a causal role. There is strong evidence for other paradigms as well, but many are unaware that these are not mutually exclusive, and pathogens are suggested as a trigger to the well established downstream processes. I recruited Dr. Omer Bender to do a PhD in my lab. Omer (DMD, M.Sc. in cellular and developmental biology) previously researched the P. gingivalis in periodontitis and diabetes, and its effect on the production of pro-inflammatory molecules. Prof. Gozes is a world-leading researcher on Alzheimer’s disease and related neurodegeneration. We are sitting together on the BIRAX healthy aging committee. She happily agreed to join the project and is working with us, providing invaluable knowledge and expertise. Budget Planning: We request 250,000$ for a year, with an option to expand the timetable to another year (without extra funding). This will allow us to fully fund Dr. Bender, so he can devote 100% of this time for this research, and hire a postdoc/technician to assist him. Additionally, our lab manager will devote 20% of her time to this project. The remaining funds will be split between mass-spectrometry services, allowing for optimal data generation, consumables, molecular biology reagents and cost of obtaining additional samples. Salaries: 100,000$ (2 people full time, lab manager 20%) Mass-spectrometry services: 75,000$ Consumables, reagents, custom plasmids for validation: 50,000$ Miscellaneous (biobanks fees, shipment of samples from abroad): 25,000$
Project budgetRequired Funding$250,000