Updated 22 December 2010. View In Memory: Mark A. Smith on the Journal of Alzheimer's Disease website.


Mark A. Smith
21 December 2010. As shocked researchers notify each other privately, the Alzforum editors are saddened to inform the community at large that Mark Smith died last Sunday.

According to the Cleveland Plain Dealer, Smith, a prolific and outspoken researcher on Alzheimer’s disease and the biology of aging, was walking home at about 2 a.m. from an early Christmas party at a local tavern, when a man, who had apparently been at the tavern as well that night, struck him from behind and left the scene. Another motorist noticed the body of a man lying in the road, notified the police, and Smith was pronounced dead at a local hospital shortly thereafter. Incredibly, the driver was later found dead in his home or his car, according to various early news reports (see, e.g., The News-Herald). Police are investigating.

Mark Smith was well known to Alzforum readers. Starting in 2002, he became a frequent commentator and co-led ARF Live discussions as early as 1999.

Born in 1965, Smith grew up in England, trained there and in Vienna, Austria, and then began his U.S. career with a postdoctoral position in 1992 in the lab of George Perry at Case Western Reserve University in Cleveland, Ohio. Smith rose through the ranks at Case Western, where he was professor of pathology. In 2006, Perry moved on to become dean at the University of Texas at San Antonio, but the two continued to work together closely. “We exchanged 20 e-mails per day and spoke daily on the phone, the last time Friday,” said Perry.

Smith and Perry coauthored some 500 papers and shared the work of editor-in-chief of the Journal of Alzheimer’s Disease. They co-edited, with Jesus Avila and June Kinoshita, the centennial book Alzheimer’s Disease, A Century of Scientific and Clinical Research, IOS Press, 1996. “Mark and I were indistinguishable in many ways. We worked on everything together,” said Perry. Indeed, a follow-up to this book, chronicling the major discoveries in AD research in the years since 1996, is already in planning; Perry will dedicate it to Smith.

Smith’s main contributions to the understanding of Alzheimer’s disease lie in the areas of oxidative stress and the cell cycle. On the former, Perry recalled that oxidative stress was mentioned before Smith’s work but was really not developed as a mechanism contributing to AD pathogenesis. “Mark established that with energy, drive, and creativity,” Perry said.

Craig Atwood, a former colleague and early collaborator of Smith’s, who is now at University of Wisconsin, Madison, noted that in time, Smith’s work on a possible reactivation of the neuronal cell cycle as a mechanism in AD may come to be seen as an equally important discovery. Starting a decade ago, Smith repeatedly questioned the predominance of the amyloid hypothesis in Alzheimer’s research (see e.g., Smith et al., 2000 and Smith et al., 2002). He delivered his criticism with irreverent British humor and sometimes self-deprecation, and was perhaps best known in the AD field for his stance paired with his work on oxidative stress. However, his research actually ranged across disciplines, from cancer to prion disease to development and neuroendocrinology. Smith also served as executive director and treasurer of the American Aging Association. “Mark’s death is a huge loss,” Atwood said.

Mark Smith leaves behind his father, two sisters, his wife Gemma Casadesus, who is an assistant professor at Case Western Reserve University, and their two young sons.

With this obituary, the Alzforum editors reach out to our wider community. Did you know Mark? Did you work with him? Hear him speak? Train with him? In this time of sorrow for Mark’s family, reach inside and share a tribute to Mark. We’ll post your mementos—pictures of shared moments, recollections sad and funny, rich and light. For their part, the Journal of Alzheimer’s Disease will gather contributions from their staff and collate them into a printed book memorializing Mark for his family and friends. The Alzforum will gladly contribute your comments to this book.—Gabrielle Strobel.

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  1. I am so sorry to hear the sad news about Mark A. Smith, whose tragic death has robbed the world of one of the most outspoken and fervent advocates for Alzheimer’s disease research. Mark’s premature death must be a painful loss for his family and friends, and they are in my prayers. I believe that the Alzheimer’s field has lost one of the most articulate and brave advocates in Mark Smith, who was never afraid to challenge views that he thought were either wrong, lacked proper foundation, or which were stifling progress. I was fortunate enough to have published several papers/reviews with Mark on ubiquilin and on the cell cycle, where I witnessed his professionalism, scientific rigor, and sharp wit. I believe that it will be our responsibility, even more so now, to bear the torch that Mark has lit and to emulate his passion and advocacy for ensuring his legacy for pursuing the correct path in finding the causes and cures for Alzheimer’s disease.

  2. I cannot believe that Mark A. Smith is not with us. He was a great thinker and visionary. I had a lot of academic interaction with him. George Perry, Mark, and I jointly edited a special issue of Current Alzheimer Research in 2006, jointly participated in a workshop in the International Society of Nephrology meeting 2009 in South Korea, and were currently editing a special issue of the Journal of Alzheimer’s Disease for 2011. We would like to dedicate this issue to Mark.

    I heard his talk on the amyloid controversy in 2006 in Singapore. All of my doctoral students received his academic support during their research programs. We had even planned a symposium in India in December 2011.

    Recently, we had announced that the National Award of Ministry of Science and Technology from the Republic of Panama would be given to Mark, who was supposed to receive it on 30 May 2011. We will bestow the award to him posthumously.

    My colleagues and I in the Republic of Panama lost a great friend, collaborator, mentor, and advisor, who had a wonderful personality and offered valuable critiques. His premature death must be a painful loss for his family. My prayers are with them. Kumar Sambamurti, Gabriel Britton, George Perry, and I will carry on Mark’s scientific spirit, and, in addition to our upcoming special issue of JAD, we will also dedicate one session of our International Symposium on Drug Discovery for Brain Disorders, to be held in the Republic of Panama, 30-31 May 2011, in memory of Mark. We had great respect for him, and are not yet able to digest this sad news.

  3. What a tragic loss of life! I did not know Dr. Smith, but I clearly remember him giving a talk at Mayo when I was a graduate student. He came into the lion's den with so many Tauists and Baptists here at Mayo, but he gave a great talk and was full of life, and I remember being struck by how persuasive he was with his (then) very controversial ideas. My thoughts are with his family—this is a terrible thing to happen at any time of the year, but especially hard at Christmastime.

  4. A dear friend to so many with so much spirit, passion for his work, his family, and his friends. His brilliance and quick wit will be greatly missed by us all. My heartfelt sorrow and prayers go out to Gemma and to their wonderful boys.

  5. I'm shocked and saddened to hear about Mark. I had the good fortune to meet Mark in 2003 when he was the scientific advisor to Voyager (now Curaxis) Pharmaceutical Corp. In 2004, I attended the AD conference in Philadelphia, and heard him speak in a forum. He wasn't afraid to speak his mind, and I was shocked when he said: "Removing beta amyloid will kill people"! He was a pioneer in his field, and now it seems that AD research is coming around to realizing that he was right. Mark put 2 and 2 together back in 2001 with Dr. Bowen and realized that the overproduction of LH later in life is harmful, and by lowering LH, there is a strong chance of stopping AD. He looked forward to rejoining Curaxis Pharmaceutical as scientific advisor now that they are commencing Phase 2b trials to prove this theory.

    Gemma, Mark made a huge impression in my life. My sympathy to you and the children.

  6. I had the privilege of meeting Mark last year, and still remember his passion, enthusiasm, zeal, and excitement for scientific research and discussions.

    This news is really disturbing. I offer my sincere condolences on the untimely death of Mark Smith. It's unfortunate that a person of Mark’s intelligence and bright future had to meet with such a cruel end. I am sure it's a great loss for everyone associated with him. May his soul rest in peace, and may his work be an inspiration to all.

  7. Mark Smith was an outstanding AD researcher, an incredibly motivated scientist, and an outspoken and interesting individual who could always be counted on to enliven any scientific conversation. His questioning of dogma and ability to raise alternative testable ideas enriched our field. This is a tragic loss, and we will miss Mark tremendously.

  8. I was lucky enough to meet Mark Smith a number of times over the past few months, having followed his work for several years. I am still in shock and deeply saddened to hear about the events of last weekend. It is almost beyond comprehension.

    The last time I saw Mark was at the end of November at a meeting in London where he characteristically (and instantaneously) spiced up the discussions and offered real insight into a variety of aspects of AD research. Hearing Mark speak really made you feel as if a difference could be made, and his passion to make that difference to the AD community was absolutely apparent from the outset.

    It is almost impossible to know what to write here, and in the absence of being able to construct a decent sentence, the following words remind me of the person I met: inspirational, talented, passionate, bold, brilliant, creative, witty, charismatic, insightful, and caring.

    My deepest sympathies go out to his family and many friends. He will be missed.

  9. Mark Smith's enormous contributions to Alzheimer's disease research are paralleled in magnitude by his challenging of entrenched schools of thought, and his willing of the scientific community to a return to objective analysis of their own data. We may well have lost decades or more in the pursuit of a cure for Alzheimer's disease. That said, his prominence in the field and his contributions to those who suffer from Alzheimer's disease pale in comparison to who he was as a man, a husband, a father, a son, a brother, and a friend. He was one for the ages, and will be sorely missed for years to come.

  10. So sorry to hear this tragic news. Losing someone who was doing their best to make a contribution to find answers to this devastating disease is a tragedy.

  11. This is a terrible loss to the field. Mark was a much-needed counter voice against the most popular theories and models of AD. He will be missed.

  12. I came to Mark’s lab as a Fulbright scholar in the fall of 2007 from a small EU country, Serbia. In the first week of my stay in Mark's lab, he challenged me to work on a hypothesis that was at the time and is still now a new paradigm of how neuronal cells are affected by Alzheimer’s disease, i.e. how cohesion impairment may affect neuronal cell cycle re-entry. So, in this regard and after 3 years of being in his lab, he has always found time, private and scientific, for lengthy discussions and encouragement to pursue new ideas. It is a truly great loss.

    If you can hear and see us: "Thank you for your kindness and encouragement."

    Vlad

  13. Those working and playing with Mark had a special knowledge, the secret of his superhuman power to get things done. It was simple: generosity of spirit, intellect and effort, all hidden under a legendary sense of humor and love of life. Mark supported everyone around him, from senior professor to beginning high school student, by instilling a confidence that all could contribute to improving the world if they had the courage to follow their data and, more importantly, their intuition. Certainly, if a coal miner’s son could be a leading scientist, it was not pedigree but perspiration and heart that would propel one forward. This knowledge permeated and touched everyone, even those who knew him only as a reviewer or meeting attendee, for it is rare for scientists to support total strangers.

    His first correspondence inquiring about a position at Case Western was filled with charisma that jumped off the page. His wit in answering ambiguous questions prepared us for what was to come. Mark was to develop a new area in Alzheimer’s disease research, but as I quickly learned when picking him up at the airport, it would have to be through golf clubs, skis, cricket and soccer equipment, because these, rather than books, filled his luggage.

    Mark, the newly arrived postdoctoral fellow, struggled with experiments and expectations at a laboratory where one could only talk about work, papers, and grants. And although I was probably the last to get it, Mark’s gift was contagious, moving the most demanding to plead his case that he would live up to expectations. I remember well relocating him to a closet, trying to reduce his salary, and many other extreme measures. Then, suddenly it happened, Mark’s talents to give brought the key collaborations and insights to establish the field. Our research group was revolutionized; traditional focus was replaced by a wide-ranging idea market. Mark changed all of us into a giving team that reached around the world. For colleagues who were low on funding or productivity, he was there to help. The cost for the aide was simple but essential: You had to believe in yourself and share your talents with others. That was Mark’s secret; the return was great. I am sometimes asked how I could work so closely with Mark that my own contribution seemed lost. Instead, it was returned a hundredfold every day. Even with death, I believe that is still true.

    By fixing cars, houses, and people, Mark was all about giving back and making the world better. He knew the privilege of the academic life rested on the efforts of the working class, and that strengthening scholarship was not just the business of science. He trusted everyone as subscribing to his secret until proven otherwise, but with data to the contrary, he would become as fierce a competitor in science as he was on the sports field.

    Our laboratory family has lost its soul, or as Sandi often says, “the idea person.” And although Beth, Peggy, and Sandi knew Mark’s legendary over-commitment, they depended on him to get it all aligned. Now it will be up to his laboratory family to build on his legacy. Their efforts in the quest for an understanding of Alzheimer’s disease must, as Mark’s, not be tied to pre-existing ideas, including our own.

    Early on, I had the great fortune of meeting Gemma and instantly feeling they were meant for each other. With time, I saw a passionate relationship develop, and then came William and Luke, who were everything to Mark. John and Rita were always there when a house needed repair, and saying, “Mark is a good lad,” a promise then, but now the life we celebrate in each of us.

  14. I am deeply shocked and saddened by the untimely, tragic loss of Mark. My condolences to Gemma and the boys, Mark's friends, relations, and colleagues. His was an irrepressible, irreverent, and impassioned spirit who will be greatly missed.

  15. No number of words can convey the impact that Mark's loss will have on our field.

    Mark truly embraced the idea of being a scientist. He was universally loved and hated for using data to defend or deny a hypothesis. We all know there are problems with any hypothesis, but it is hard to admit that such problems exist, much less try to get funding to address them.

    Mark was outspoken, and I will never forget him for it. Perhaps this is the character of a leader that is so sorely missing in the "spin doctor" world of science today.

  16. I am very saddened to learn of the death of Professor Mark Smith. I had the privilege to meet him at three successive ICAD meetings. He had a unique and wonderful personality. The scientific community has lost a giant of medical research on Alzheimer's disease. I offer my deeper condolences to his wife, children, and entire family.

  17. I first met Mark when we sat together on a shuttle bus at a meeting many years ago. I was struck by his energy, enthusiasm and ability to look at problems in a novel way. We kept in touch over the years and I placed a high value on our interactions and meetings. His passing is a huge loss to science and I send my sincere condolences to his family and friends.

  18. I am very sad to hear about death of Mark Smith. We have lost a great scientist in aging and health. As mentioned, Smith worked on a possible reactivation of the neuronal cell cycle as a mechanism in AD and the predominance of the amyloid hypothesis in Alzheimer’s research (e.g., Smith et al., 2000, and Smith et al., 2002). His discoveries and questions have aroused various new hypotheses in AD in addition to the amyloid cascade hypothesis(see diagram). In the amyloid cascade hypothesis, AD is purported to be a clinico-pathological syndrome in which different gene defects can lead directly, or indirectly, to altered APP expression or proteolytic processing, or to changes in Aβ stability or aggregation. These result in a chronic imbalance between Aβ production and clearance, and the gradual accumulation of aggregated Aβ initiates a complex, multistep cascade that includes gliosis, inflammatory changes, synaptic changes, tangles, and transmitter loss.

    I must commend Mark for his contributions to medical research on AD. His passing away is indeed a giant loss, and I offer my deep condolences to his family. I also support the idea that the Journal of Alzheimer’s Disease gather contributions from their staff and collate them into a printed book memorializing Mark for his family and friends.

    References:

    . Arson. Tracking the culprit in Alzheimer's disease. Ann N Y Acad Sci. 2000;924:35-8. PubMed.

    . Predicting the failure of amyloid-beta vaccine. Lancet. 2002 May 25;359(9320):1864-5. PubMed.

  19. I was Mark's graduate student. I want to please request that all of his friends, associates, and admirers contribute to a special hot topic issue, "Polyphenolic Antioxidants in Health Disease and Aging," in Immunology, Endocrine & Metabolic Agents in Medicinal Chemistry. The issue will honor both Mark and the late Jim Joseph. I worked with and knew both well, and they will be missed for their contributions to science.

    Details of the hot topic issue can be found at Bentham Science Publishers.

  20. I did not know Dr. Smith well enough but I had the chance to publish a paper with him a couple of months before he passed away. I believe he was open minded and a visionary man. I would like to tell his family that I am so sorry for their loss.

References

Webinar Citations

  1. Apoptosis in Alzheimer Disease

Paper Citations

  1. . Arson. Tracking the culprit in Alzheimer's disease. Ann N Y Acad Sci. 2000;924:35-8. PubMed.
  2. . Predicting the failure of amyloid-beta vaccine. Lancet. 2002 May 25;359(9320):1864-5. PubMed.

Other Citations

  1. Mark A. Smith

External Citations

  1. In Memory: Mark A. Smith
  2. Cleveland Plain Dealer
  3. The News-Herald
  4. Mark Smith
  5. American Aging Association

Further Reading

No Available Further Reading