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The Value of Writing a Book: Trying to Cure Alzheimer’s
Reading the headlines about the failed clinical trials trying to cure Alzheimer’s disease over the past 10 years has been frustrating for everyone including the patients, their families, researchers, the company sponsors, and their stock holders. For me, it was another dart to my heart noting that they are after the wrong target. Why won’t investigators give my work a shot? One needs to prevent the amyloid from leaking through a damaged blood-brain barrier into the brain, and then into susceptible neurons before they die, not just block the production of amyloid, which happens to be required for many normal processes including memory and learning.
I’ve published many papers in this area and to this date, I haven’t read any contrary work, which made me more and more frustrated not to mention confident. Once we are able to clearly define the amyloid plaque types (which are still uncharacterized), then we can learn that lethal amounts of amyloid enter the neurons, which die forming the hallmarked dense-core amyloid plaques. Therefore, removing the amyloid plaque is a fruitless objective.
I want the book to provide a platform for all to embrace, for the message to integrate into their open minds, and for them to ‘take the ball and run with it’.
I needed to find a way to get my message out without writing another simple review. A way to take the reader along the ride on how I embarked in the field, and what led me to compose the experiments to mold my hypothesis of how neurons die leading to Alzheimer’s disease, so that they too can continue my work. I would make the case that I was one of the first researcher to draw relevance to intraneuronal amyloid, which at that time, only drew skepticism. I was and continue to be the only one who drew the connection between amyloid-burdened neurons and dense-core amyloid plaques that one leads to the other. I was also one of the first to show that amyloid plaques do not have similar etiologies and that some are actually inconsequential or benign to impacting neuronal loss and therefore cognitive impairment. Furthermore, it became more and more difficult for me to read the classical story that amyloid plaques form from the ‘extracellular deposition’ of amyloid between neurons that eventually grow to kill neighboring neurons, which is presumed more fact than hypothesis.
I’ve co-edited a work on biomarkers in drug discovery, but I had no experience on such a task as I didn’t’ know where to start or who to contact. Then it occurred to me to contact Elsevier where I had many peer-reviewed, Alzheimer’s disease-related publications. And so I did, and after their reviewing process, we agreed to a deadline, and then I was off to the races, as they say. For the next 6 months, all of my free time was dedicated to writing.
At times, my fingers couldn’t keep up with my mind, and I could feel all of the passion juices flowing again, re-reading my old papers was like flipping through a college yearbook with each page generating all sorts of memories. I could see in my mind all those experiments, reading those hundreds of microscopic slides, giving the many presentations, and all of the discussions, and especially those times when confronting those challenges to my story. At times while typing, I had to get up and take a walk as the memories were getting intense again, but all I could say to myself was, ‘hey, no one solved it yet, so all bets are still on the table’.
In fact, I started to question just who is an authority on Alzheimer’s disease research anyway; who can really be a key opinion leader in the field? Those researchers with the most funding? As far as I can tell, most hypotheses have failed, and what the field really needs fresh, objective, naïve minds that may benefit from this book. After all, I started the work in this area, even when reviewers and peers would challenge the intraneuronal amyloid as mere background, or non-specific staining, or that there was so little, that it couldn’t possibly impact neuronal health. If there was anyone to talk about intracellular amyloid leading to neuronal death, it would be me, and chronically my work would show everyone just how I derived at this hypothesis. Collating a cohesive story could be much more powerful than simply providing a litany of singular experiment reports in peer-review journals.
This hypothesis of how Alzheimer’s disease begins, can also explain why it remains incurable. Once the neurons die as dense-cored amyloid plaques, they cannot be rescued. This book can provide insight into this explanation, while providing the reader other aspects of the work to further investigate.
I want the book to provide a platform for all to embrace, for the message to integrate into their open minds, and for them to ‘take the ball and run with it’. That would be my goal, and I can only hope that as more and more investigators read it, they will agree that protecting the blood-brain barrier via diet, via exercise, and annual examination monitoring is the first level of defense. A healthy blood-brain barrier will prevent the unregulated entry of vascular-derived amyloid from entering the brain to upset the delicate balance of CNS-derived amyloid in-place to control normal learning and memory.
About the author:
Michael R. D’Andrea received his PhD in Cell and Developmental Biology and his MS in Molecular Biology at Rutger’s University, New Brunswick, NJ, and his BA in Psycho-Biology at Western Maryland College, Westminster, MD. His dissertation work utilized molecular and histological assays to study the regulation of DNA topoisomerases in human cancers. His earlier career concerned the use of the high magnification electron microscopy to support oncogenesis in preclinical models, and then moved into a new field where he and his peers co-invented the chorionic villus sampling method at Thomas Jefferson for clinical chromosomal analysis. In the late 1980s and early 1990s, he mastered immunohistochemical methods at the light and electron microscopy levels when he began publishing his work in scientific journals.
However, it wasn’t until the mid-1990s, while working at Johnson & Johnson’s Pharmaceutical Research & Development as the Target Validation Team Leader, did he become engaged in Alzheimer’s disease (AD) research. His Team was responsible for supporting target discovery and validation, while supporting biomarker discovery in preclinical and experimental models using genomic, proteomic, and histopathological methods across many therapeutic areas and was honored with over a dozen Leadership and Scientific awards. Currently, he has over 100 scientifically peer-reviewed scientific publications and invited reviews, about a third of which concern the neuropathology of AD, and holds 11 scientific patents. He has reviewed hundreds of papers for many scientific journals, reviewed international grants in the AD field, and is currently on the editorial board of the journal, Biotechnic & Histochemistry.
He has been invited to speak at numerous International, National, and Regional meetings, as well as at Universities and other companies to discuss his novel observations concerning the origin of amyloid plaques, the existence of various plaque types, and most recently that AD is also an autoimmune disease; all of which is presented in this book. Recently, Michael established a contract research company, Slidomics, LLC (www.slidomics.com) to apply his histopathological and target validation expertise by providing high quality data and analysis much like what you see in this book.
Michael is author of Intracellular Consequences of Amyloid in Alzheimer’s Disease and Bursting Neurons and Fading Memories.
The scientific study of the nervous system is entering a new golden age. Researchers and clinicians continue to advance the treatment of conditions such as Alzheimer’s syndrome, Parkinson’s disease, epilepsy, and traumatic brain injury. Public initiatives like the federal Brain Research Through Advancing Innovative Neurotechnologies (BRAIN) program in the United States, announced in April 2013, ensure that funding and resources will continue to be applied to this rapidly growing field. Elsevier’s journals, books, eBooks, online references, and tools are respected around the world for everything from physiology and pathology to behavioral genetics and nerve repair. Our publications are a gateway to the latest advancements in neuroscience research and leading-edge data for professionals, students, and academics alike.