Paul Stephen Aisen, MD, is an internationally recognized Alzheimer's disease researcher and the founding director of the University of Southern California Alzheimer's Therapeutic Research Institute (ATRI). [1] Since the 1990s, Aisen has been a leading figure in the field of Alzheimer's disease research, developing novel methodologies and directing large-scale clinical trials to develop groundbreaking medications. [2] A physician, he has played a major role in our understanding of the progression of Alzheimer's disease. Research that he co-authored led to the U.S. Food and Drug Administration's approval of some of the world's first Alzheimer's disease-modifying drugs. He started his career as a rheumatologist and then made Alzheimer's disease his focus. Aisen serves as the Epstein Alzheimer's disease director's chair and a professor of neurology at the Keck School of Medicine of USC. He is based out of ATRI's San Diego innovation campus. [3]
Aisen is known for his collaborative approach to medical research, bringing together the public and private sectors to accelerate development of effective treatments for Alzheimer's disease. He is an advocate for data transparency and sharing research findings to promote problem-solving. An example of his thinking lay in the mission of the National Institutes of Health-funded Alzheimer's Clinical Trials Consortium (ACTC), which ATRI oversees under his leadership. ACTC works cooperatively to conduct Alzheimer's disease clinical trials across more than 30 member sites in the United States. [4] The mission of ACTC is to "provide an optimal infrastructure, utilizing centralized resources and shared expertise, to accelerate the development of effective interventions for Alzheimer's disease and related disorders." [5] Research data from ATRI and ACTC is shared with the international community. [6]
Aisen is a strong proponent of advancing therapeutics at each stage of Alzheimer's disease. He has long proposed launching intervention strategies before the onset of symptoms, while also pursuing therapies at later stages. He has stated that dementia is the end stage of Alzheimer's disease, when extensive irreversible damage is already present. [7] He supports the development of therapies that forestall and even prevent Alzheimer's disease before it can take hold. The idea is to develop therapies aimed at stopping the buildup of plaques and tangles that disrupt brain cell function.
Aisen is one of the most often-cited authors when it comes to Alzheimer's-related research. Among the most important of his research papers was an article he authored reporting the findings of a trial leading to FDA approval of the Japanese pharmaceutical company Eisai's drug lecanemab (known commercially as Lequembi) in 2023. The drug targets and removes amyloid plaques, which are proteins in the brain that contribute to causing the disease. ATRI collaborates with the American pharmaceutical company Lilly on the continuing development of donanemab (known commercially as Kinsula), which targets removal of amyloid plaques to slow decline in memory and thinking. [8]
Aisen advocates for slowing down the progression of Alzheimer's disease and also preventing it altogether. He has stated that he believes the mission of preventing the disease can be achieved by 2035. [9] This could be accomplished through blood tests that search for certain abnormalities before amyloid plaques can build up in the brain. By intervening at the earliest stage, tens of millions of people predisposed to Alzheimer's disease can live out the long, full lives they deserve.
Aisen began a solo private practice in internal medicine and rheumatology in New York and joined the faculty of Mount Sinai Medical Center in 1994. He had been recruited to provide geriatric medical care to patients receiving treatment for memory impairment. [10] This work helped Aisen identify his ultimate career focus of studying and researching Alzheimer's disease and related conditions. In 1999, he was recruited to join the Georgetown University School of Medicine as a professor of neurology and medicine. There, he founded the Memory Disorders Program, a clinical and research program for Alzheimer's disease and related disorders. [11]
In the early 2000s, Aisen worked on research studies to identify therapeutic targets and biomarkers for Alzheimer's disease and related disorders. He also designed and directed research as part of multi-location therapeutic trials. He became vice chair of Georgetown University's Department of Neurology in 2004. [12]
The following year, Aisen was asked by leaders at the National Institutes of Health, as well as Leon Thal, MD, one of the world's leading Alzheimer's disease researchers, to take on a role as associate director of the national Alzheimer's Disease Cooperative Study (ADCS). Thal had built it from an $18 million federal grant-funded operation in 1991 to a more than $100 million program coordinating and conducting trials at dozens of institutions from the homebase at University of California San Diego (UCSD). Among other work, ADCS coordinated studies on Alzheimer's disease drugs like solanezumab. [13] After Thal died in 2007, Aisen as asked to serve as Director of the ADCS at UCSD, where he was also a professor in the Department of Neurosciences.
In 2015, Aisen founded ATRI, the San Diego-based satellite of the Keck School of Medicine of USC. ATRI's mission is to accelerate the development of effective treatments for Alzheimer's disease through innovative, collaborative, multicenter trials. Aisen and his team at ATRI rigorously study new compounds that could be used to prevent the advancement of Alzheimer's disease-related brain damage and eventually offer prevention strategies for asymptomatic people. They also work on a variety of treatments for those experiencing symptoms.
After Aisen left UCSD for USC in 2015, the two universities ended up in court over the question of which would house the Alzheimer's Disease Cooperative Study. At the time, the study involved six ongoing clinical trials and extensive data. Some aspects of data management were temporarily settled in 2016. [14] A final settlement was reached in 2019, with USC agreeing to pay UCSD $50 million and make a public statement that is actions "did not align with the standards of ethics and integrity which USC expects of all its faculty, administrators, and staff." [15] Today, the two universities work together on Alzheimer's disease research.
Aisen and the ATRI team have many working partnerships, including with Harvard University, Mayo Clinic, and the University of California, San Francisco, among others.
In addition to managing the ACTC, Aisen and his team at ATRI coordinate the Alzheimer's Disease Neuroimaging Initiative (ADNI), an important longitudinal observational study of Alzheimer's disease. ADNI is widely regarded to have pioneered real-time sharing of scientific data, an approach that has resulted in over 2,800 publications. [16]
Under Aisen's leadership, ATRI also led the Anti-Amyloid Treatment in Asymptomatic Alzheimer's (A4) Study, the first and largest clinical trial of pre-symptomatic AD. Comprehensive A4 study data is made widely available to further the advancement of the field and is already yielding key insights.
Aisen has made contributions across the medical research field. He serves as a member of the Organizing Committee of the Clinical Trials on Alzheimer's Disease (CTAD), which has put on important annual industry conferences in this area of research for more than 14 years. Aisen collaborates with other members to ensure that the meeting is focused on Alzheimer's disease therapeutic trials with key leaders from around the world. [17]
Aisen is also editor-in-field of the Journal for the Prevention of Alzheimer's Disease, which publishes reviews, original research articles and short reports to improve knowledge in the field of Alzheimer's disease prevention. [18]
To further patient safety and the development of effective therapeutics, Aisen has served as a consultant, advisor or contributor for pharmaceutical companies Eli Lilly, [13] [19] Janssen, [20] and Eisai, as well as smaller biotech companies exploring alternative approaches to AD like Anavex Life Sciences, [21] Proclara, [22] CohBar, [23] and NeuroPhage, [24] as well as nonprofits like ACT-AD. [25] He is a principal investigator in the Alzheimer's Disease Neuroimaging Initiative. [26]
Aisen earned his Bachelor of Arts degree in biochemistry and molecular biology from Harvard University and his medical degree from Columbia University. He completed his residency at Case Western Reserve University and Mount Sinai Medical Center in New York, where he also served as chief medical resident. Aisen trained further through a fellowship in rheumatology at New York University. [27]
Aisen is recognized as one of the world's top-ranked experts in Alzheimer's disease. [28] He has an h-index of 149, according to Google Scholar, [29] which measures an author's productivity and citation impact compared to others. He has published more than 500 peer-reviewed papers and has been named to the Clarivate Highly Cited Researchers list every year since 2021. [30]
Aisen was honored as the Alzheimer's Association San Diego/Imperial Chapter's 2024 Research Champion for his role as a "leading figure in Alzheimer's disease (AD) research for three decades, having developed novel methodologies and directed many large therapeutic trials." [31]
Among Aisen's most cited works are: