First Discovery


Alzheimer’s disease got the name from Dr. Alois Alzheimer. He first noticed changes in the brain tissue of a woman who had died of an unusual mental illness. Her symptoms included memory loss, language problems, and unpredictable behavior. After she died, he examined her brain and found many abnormal clumps (now called amyloid plaques) and tangled bundles of fibers (now called neurofibrillary, or tau, tangles).

Amyloid plaques
Neurofibrillary, or tau, tangles

These plaques and tangles in the brain are still considered some of the main features of Alzheimer’s disease. Another feature is the loss of connections between neurons in the brain. Neurons transmit messages between different parts of the brain, and from the brain to muscles and organs in the body.


Emerging Research


Steps Toward Treatment


Advancement in Technology


The Alzheimer’s Disease Neuroimaging Initiative (ADNI) was funded by National Institute of Aging (NIA) plus contributions from pharmaceutical companies in 2004 to optimize biomarker assessments in support of AD therapeutic trials. This multicenter project would grow to be conducted across 63 sites studying three cohorts, cognitively normal individuals, those with mild cognitive impairment and those with mild AD dementia, with MRI, lumbar puncture for spinal fluid analysis, and cognitive and clinical assessments longitudinally. Amyloid PET imaging was added to the ADNI protocol in 2005, and tau PET was added in 2015. Remarkably, ADNI shares all data collected as soon as it is quality-controlled; this aggressive data sharing has resulted in over 2000 peer-reviewed publications using ADNI data. The coordinating center for ADNI moved to USC ATRI in 2015. ADNI data has been instrumental to the design of most therapeutic trials in the field. The latest application to continue ADNI has been submitted.


Nationalizing AD Prevention


The National Plan establishes five ambitious goals to both prevent future cases of alzheimer’s disease and related dementias (ad/adrd).

1 – Prevent and Effectively Treat Alzheimer’s Disease by 2025.
2 – Optimize Care Quality and Efficiency.
3 – Expand Supports for People with Alzheimer’s Disease and Their Families.
4 – Enhance Public Awareness and Engagement.
5 – Track Progress and Drive Improvement.


Foundation of ATRI & ACTC


A major milestone was the launch of the Anti-Amyloid treatment in Asymptomatic Alzheimer’s (A4) Study.  A4 is the first multicenter trial in sporadic preclinical (pre-symptomatic) Alzheimer’s disease (AD). The idea for this project arose from analysis of longitudinal observational data from the Alzheimer’s Disease Neuroimaging Initiative (ADNI) that indicated that amyloid elevation in brain in clinically normal individuals is associated with subtle cognitive and biomarker evidence of decline.  Thus ‘preclinical AD’ may be the optimal stage at which to intervene with anti- amyloid therapies, with sensitive cognitive tests as well as secondary biomarker measurements as outcomes to establish efficacy. A4 was initially funded as a project of the ADCS.  Solanezumab, a monoclonal antibody against monomeric amyloid peptide was selected as the therapeutic, and a public private partnership with Eli Lilly and NIA was established to carry out the trial, with additional funding contributed by philanthropic groups. A4 transitioned to USC ATRI in 2015 and was fully enrolled with 1169 randomized participants across 67 sites by the end of 2017. It will be completed near the end of 2022. In a first for a Phase 3 trial, A4 pre- randomization data, which provides the largest dataset on amyloid accumulation in clinically normal individuals, was publicly released one year after completion of enrollment.


The Alzheimer’s Therapeutic Research Institute (ATRI) was founded by Paul S. Aisen, MD  and a group of about 40 faculty and staff who had been working together for many years at the Alzheimer’s Disease Cooperative Study (ADCS), which at the time was the primary National Institutes of Health (NIH) funded program conducting clinical trials in Alzheimer’s disease (AD).  

Located in San Diego and part of the University of Southern California (USC) Keck School of Medicine, the mission of ATRI is to accelerate the development of effective therapies for AD.  

ATRI was designed to facilitate effective academic-industry collaborations with major administrative support from USC.  Its structure is unique among USC institutes. The faculty members, while pursuing their own independent research, are all actively involved in the institute’s primary mission, and so constitute a well-aligned research team. The expertise at ATRI is multidimensional, with world renowned scientists and a research team across multiple disciples working together within a team science environment in the systematic pursuit of establishing the most innovative and collaborative global clinical trials program in AD therapeutics. This highly experienced research team, with expertise in biomarkers, biostatistics, clinical monitoring, clinical operations, finance, informatics, regulatory, recruitment, and medical safety, and an independent Data and Safety Monitoring Board, allows ATRI to efficiently conduct international multicenter clinical trials and other large clinical research studies . The embedded USC human resources and contracting enable efficient large-scale operations.


In 2016, NIA released a funding opportunity announcement inviting applications for a new academic network called the Alzheimer’s Clinical Trial Consortium (ACTC).  The announcement incorporated many new ideas resulting from the decades of experience in the field, including the value of a central institutional review board, standing support for trial sites and separation of project funding from the parent grant mechanism, among others. The first ACTC grant was awarded to a team of investigators at three institutions, USC, Harvard and the Mayo Clinic.


In the first five years since its formation, ATRI has established itself as a global Alzheimer’s disease research institute conducting high quality research attracting funding from the public and private sectors.  The initial team of 40 has grown to include seven faculty with academic appointments at the USC Department of Neurology and approximately 170 research and administrative staff.  

Major collaborations with the National Institutes of Health (NIH), Alzheimer’s Association and several industry partners make ATRI one of the largest and most successful independent programs, both at USC and elsewhere.  ATRI continues to be an evolving enterprise; in terms of clinical trials, grants and publications.


Modern Research


The U.S. Food and Drug Administration approved Aduhelm (aducanumab) for the treatment of Alzheimer’s, a debilitating disease affecting 6.2 million Americans. Aduhelm was approved using the accelerated approval pathway, which can be used for a drug for a serious or life-threatening illness that provides a meaningful therapeutic advantage over existing treatments.

Aduhelm represents a first-of-its-kind treatment approved for Alzheimer’s disease. It is the first new treatment approved for Alzheimer’s since 2003 and is the first therapy that targets the fundamental pathophysiology of the disease. Read more about this historic approval here.


In January, 2022, U.S. Food and Drug Administration approved Leqembi (lecanemab-irmb) via the Accelerated Approval pathway for the treatment of Alzheimer’s disease. Leqembi is the second of a new category of medications approved for Alzheimer’s disease that target the fundamental pathophysiology of the disease. Read more about this milestone in the ongoing fight to effectively treat Alzheimer’s disease here.


A joint gift to USC and the University of California, San Diego, totaling $50 million from the Epstein Family Foundation will drive Alzheimer’s research and accelerate the search for treatments and a cure.

The generous donation establishes the Epstein Family Alzheimer’s Research Collaboration at USC and UC San Diego. The gift will be split evenly, with $25 million going to each institution. The funding will support existing research at each university and will spark new collaborative efforts to discover effective therapies for Alzheimer’s disease.


In cooperation with Carolyn Meltzer,  Dean of the Keck School of Medicine of USC, and Berislav Zlokovic, Director, Zilkha Neurogenetic Institute the Alzheimer’s Therapeutic Research Institute (ATRI) successfully recruited our long-term collaborator Robert Rissman, Director of ATRI Biomarker Laboratory and Biorepository to establish a Neuroscience Translational Research Division.  This change greatly expands the scope of ATRI to include basic science translational research in models of disease that can serve as preclinical work for future therapeutics.