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Allen Roses
Jared Lazarus/Duke Photography
Obituary
Allen Roses Neurologist who first identified genetic risk factor for Alzheimer’s disease. Born on Feb 21, 1943, in Paterson, NJ, USA, he died from a heart attack on Sept 30, 2016, in New York, NY, USA, aged 73 years. When Duke University neurologist Allen Roses and his team first identified a gene that increased the risk for developing Alzheimer’s disease, they were met with scepticism. It was the late 1980s and the prevailing hypothesis then was that the disease results from amyloid protein fragments building up in the brain and causing memory loss. Roses argued that β-amyloid plaques were the result of the disease rather than its cause. While researchers, funding agencies, and pharmaceutical companies continued to focus on amyloids, Roses homed in on two genes: APOE and TOMM40. APOE is now used in diagnosing patients with the disease and TOMM40 is a target for drugs to delay the onset of the disease. “Allen Roses was amongst the first academics to realise the power of molecular genetics and made Duke a centre for this type of study, making real contributions to myotonic dystrophy and CMT [Charcot-Marie-Tooth] research amongst others before making what became his signature contribution: the identification of APOE as a risk factor for Alzheimer’s disease”, says John Hardy, Head of the Department of Molecular Neuroscience at University College London’s Institute of Neurology. Hardy adds that “Allen was a larger than life character, whose principal delight was taking the position opposite to conventional wisdom. Usually this meant he was wrong, but his gadfly approach sometimes 2232
paid off with big findings, and APOE is clearly perhaps the most important risk allele in the human genome.” In 1993, Roses reported in the Proceedings of the National Academy of Sciences that the APOE4 variant of apolipoprotein is associated with an increased risk of Alzheimer’s disease. The finding was controversial and Roses fought for research funding to explore it further. He left Duke in 1997 to join what is now GlaxoSmithKline to continue his work on APOE and to oversee the company’s research in genetics. 10 years later, he returned to Duke to direct the Deane Drug Discovery Institute. In 2009, his team discovered variations in the gene TOMM40 that disrupt the function of mitochondria in neurons and influence the age of onset for Alzheimer’s disease. Roses postulated that the gene can inhibit mitochondria from metabolising glucose and oxygen, starving neurons of the energy they need to maintain their structure and function. In the late 2000s, Roses founded several biotechnology companies to commercialise some of his findings. One of them, Zinfandel Pharmaceuticals, is working with Takeda to investigate APOE, TOMM40, and age as biomarkers for Alzheimer’s risk and progression, and to evaluate whether the drug pioglitazone can be used to postpone the onset of mild cognitive impairment. “He was one of the very few people who made an inroad in our understanding of Alzheimer’s. It will likely lead to better understanding and something that can ultimately help us to overcome the disease”, says Wolfgang Liedtke, Professor of Neurology at Duke University. Roses held several positions at Duke, including Professor of Neurology and Neurobiology, Chief of Neurology at Duke Medical Center, founding Director of the Joseph and Kathleen Bryan Alzheimer’s Disease Research Center, and Director of the Center for Human Genetics. In addition to his work on Alzheimer’s disease, he identified chromosomal locations for Parkinson’s disease, amyotrophic lateral sclerosis, and muscular dystrophy. “His countenance reigned over Duke neurology”, says Carol A Colton, a Professor in Neurology at Duke. ”He was a bulldog and pugnacious but that fighting spirit wasn’t directed against people but at solving tough problems like neurodegenerative diseases.” Roses graduated from the University of Pittsburgh in 1963 and received his medical degree from University of Pennsylvania 4 years later. He completed his residency at Columbia University and at Duke, and served as a doctor in the US Air Force in Vietnam. He is survived by his wife, Ann Saunders; daughters, Stephanie Roses, Maija Roses, Joanna Roses Ryan, and Michelle Roses Holleman; his sister, Estelle Irizarry; and four grandchildren. In September, he gave a Duke seminar on the use of genetics in treating patients and directed much of his talk to students in the room, says Colton. “He expected medical students to understand that it was also their responsibility to challenge what they learned and to look for new ideas and new ways to investigate human disease.”
Alison Snyder www.thelancet.com Vol 388 November 5, 2016
Obituary
Allen Roses Neurologist who first identified genetic risk factor for Alzheimer’s disease. Born on Feb 21, 1943, in Paterson, NJ, USA, he died from a heart attack on Sept 30, 2016, in New York, NY, USA, aged 73 years. When Duke University neurologist Allen Roses and his team first identified a gene that increased the risk for developing Alzheimer’s disease, they were met with scepticism. It was the late 1980s and the prevailing hypothesis then was that the disease results from amyloid protein fragments building up in the brain and causing memory loss. Roses argued that β-amyloid plaques were the result of the disease rather than its cause. While researchers, funding agencies, and pharmaceutical companies continued to focus on amyloids, Roses homed in on two genes: APOE and TOMM40. APOE is now used in diagnosing patients with the disease and TOMM40 is a target for drugs to delay the onset of the disease. “Allen Roses was amongst the first academics to realise the power of molecular genetics and made Duke a centre for this type of study, making real contributions to myotonic dystrophy and CMT [Charcot-Marie-Tooth] research amongst others before making what became his signature contribution: the identification of APOE as a risk factor for Alzheimer’s disease”, says John Hardy, Head of the Department of Molecular Neuroscience at University College London’s Institute of Neurology. Hardy adds that “Allen was a larger than life character, whose principal delight was taking the position opposite to conventional wisdom. Usually this meant he was wrong, but his gadfly approach sometimes 2232
paid off with big findings, and APOE is clearly perhaps the most important risk allele in the human genome.” In 1993, Roses reported in the Proceedings of the National Academy of Sciences that the APOE4 variant of apolipoprotein is associated with an increased risk of Alzheimer’s disease. The finding was controversial and Roses fought for research funding to explore it further. He left Duke in 1997 to join what is now GlaxoSmithKline to continue his work on APOE and to oversee the company’s research in genetics. 10 years later, he returned to Duke to direct the Deane Drug Discovery Institute. In 2009, his team discovered variations in the gene TOMM40 that disrupt the function of mitochondria in neurons and influence the age of onset for Alzheimer’s disease. Roses postulated that the gene can inhibit mitochondria from metabolising glucose and oxygen, starving neurons of the energy they need to maintain their structure and function. In the late 2000s, Roses founded several biotechnology companies to commercialise some of his findings. One of them, Zinfandel Pharmaceuticals, is working with Takeda to investigate APOE, TOMM40, and age as biomarkers for Alzheimer’s risk and progression, and to evaluate whether the drug pioglitazone can be used to postpone the onset of mild cognitive impairment. “He was one of the very few people who made an inroad in our understanding of Alzheimer’s. It will likely lead to better understanding and something that can ultimately help us to overcome the disease”, says Wolfgang Liedtke, Professor of Neurology at Duke University. Roses held several positions at Duke, including Professor of Neurology and Neurobiology, Chief of Neurology at Duke Medical Center, founding Director of the Joseph and Kathleen Bryan Alzheimer’s Disease Research Center, and Director of the Center for Human Genetics. In addition to his work on Alzheimer’s disease, he identified chromosomal locations for Parkinson’s disease, amyotrophic lateral sclerosis, and muscular dystrophy. “His countenance reigned over Duke neurology”, says Carol A Colton, a Professor in Neurology at Duke. ”He was a bulldog and pugnacious but that fighting spirit wasn’t directed against people but at solving tough problems like neurodegenerative diseases.” Roses graduated from the University of Pittsburgh in 1963 and received his medical degree from University of Pennsylvania 4 years later. He completed his residency at Columbia University and at Duke, and served as a doctor in the US Air Force in Vietnam. He is survived by his wife, Ann Saunders; daughters, Stephanie Roses, Maija Roses, Joanna Roses Ryan, and Michelle Roses Holleman; his sister, Estelle Irizarry; and four grandchildren. In September, he gave a Duke seminar on the use of genetics in treating patients and directed much of his talk to students in the room, says Colton. “He expected medical students to understand that it was also their responsibility to challenge what they learned and to look for new ideas and new ways to investigate human disease.”
Alison Snyder www.thelancet.com Vol 388 November 5, 2016