Four decades of Alzheimer's disease discoveries, data, and research resources: The NIH Alzheimer's Disease Research Center Program

Abstract

The Alzheimer's Disease Research Centers (ADRC) program, funded by the National Institute on Aging (NIA), is a national network for conducting cutting‐edge basic, clinical, and translational Alzheimer's disease (AD) and AD‐related dementias (ADRD) research. ADRCs collect clinical, biomarker, neuroimaging, and autopsy data on thousands of longitudinally followed research participants and the well‐characterized data and samples generated by the ADRCs are readily available to the research community. Beyond conducting research, the primary objectives of the ADRC program are to train the next generation of multidisciplinary AD/ADRD researchers and share information with the public, including the latest findings and opportunities to participate in clinical studies. This article provides an overview of the 40‐year history of the ADRC program, from its establishment by Congress in 1984 to now, highlighting the AD/ADRD scientific achievements enabled by the ADRCs, the data, samples, and resources that ADRCs provide, and future directions for the program.

Highlights

• This article summarizes the history and infrastructure of the Alzheimer's Disease Research Center (ADRC) program.

• It describes ADRC contributions to the wider research field of neurodegenerative diseases.

• It highlights scientific achievements over the past 40 years that were enabled by the research, resources, and data contributions of ADRCs

1. INTRODUCTION

The National Institute on Aging (NIA) Alzheimer's Disease Research Center (ADRC) program is a leading national and global resource for research on Alzheimer's disease (AD) and AD and related dementias (ADRD). The ADRC network is an intentionally integrated infrastructure designed to foster close collaboration and advance AD/ADRD research in the United States, with substantial global impact on the broader field of neurodegenerative disease research. The principal objectives of the ADRC program are to (1) conduct cutting‐edge basic, clinical, and translational multidisciplinary research; (2) train the next generation of researchers; and (3) provide the public, including care providers, with information about the latest research findings, access to support services, and opportunities to participate in research. ADRC investigators aim to better understand neurodegenerative disease mechanisms and symptom heterogeneity, increase the research use of real‐world clinical information, identify early risk and protective factors, and accelerate translational research advances into clinical practice. This paper will provide a history of the ADRC program, summarize the data and resources ADRCs provide, and highlight AD/ADRD scientific achievements over the past 40 years that were enabled by the research, resources, and data contributions of ADRCs.

In 1984, Congress authorized the formation of the Alzheimer's Disease Center (ADC) program, now known as the ADRC program, under the Public Health Service Act, Section 445. ¹ The ADRC program was the first center program that was funded through NIA, which was established as an institute in 1974. The first five ADCs were designated by Congress as National Institutes of Health (NIH) Centers of Excellence ² and awarded to Harvard University, Johns Hopkins University, Mount Sinai Medical School, University of Southern California, and the University of California at San Diego. Today, the ADRC program spans much of the United States, currently with 37 individual ADRCs across 25 states. All ADRCs collect and share clinical, neuropsychological, and autopsy data on all research participants using a standardized protocol known as the Uniform Data Set (UDS). ³ The research would not be possible without the commitment of tens of thousands of research participants across the country who have given their time to attend annual in‐person visits and, in many cases, also agreed to donate their brains upon death. The combination of longitudinal annual visits, multimodal data collection, sample donations, brain imaging over time, and brain autopsy – with all data made available to researchers around the world – makes this unique program one of the strongest contributors to global research on dementia.

When the ADRC program was established, little was known about AD. In 1984, it was not possible to diagnose the disease until after death (autopsy required), it was not possible to distinguish between other causes of dementia or whether a person had more than one, and so it was virtually impossible to develop disease‐modifying treatments. Much has changed in the past four decades. Major improvements in diagnosis, better screening tools, and increased public and clinician awareness have helped identify many cases that previously went undetected and identify them earlier in the disease process. AD research is now largely focused on risk and mitigation factors as well as developing and validating specific biomarkers to predict and track disease progression. Today, AD can be diagnosed years before onset of symptoms, there are a range of diagnostics, therapeutics, and treatments in development, and US Food and Drug Administration (FDA) approval has been granted to disease‐modifying therapeutics and a blood‐based diagnostic.

While substantial progress has been made in diagnostics and therapeutics, increases in lifespan combined with an aging baby boomer population have resulted in a larger population reaching high‐risk ages. The number of people in the United States living with AD has risen to an estimated seven million. ⁴ The ADRC program now emphasizes studying the full spectrum of the disease, from normal aging to mild cognitive impairment (MCI) and dementia, including comparing and understanding the overlap of AD and other neurodegenerative illnesses. Importantly, the ADRC program has deepened and broadened scientific knowledge about the many causes of dementia in addition to amyloid and tau. Thanks in large part to research in ADRCs, we now recognize that most older adults have multiple co‐occurring pathologies rather than a single disease driving dementia symptoms. Recognition of the many complexities of the causes and risk factors of dementia is enabling rapid advancement toward precision medicine.

2. AD/ADRD RESEARCH ADVANCEMENTS INVOLVING ADRCs

The impact of the ADRC program on neurodegenerative disease research over the past 40 years has been substantial. Several landmark scientific breakthroughs that have fundamentally advanced our understanding of AD/ADRD can be traced directly to ADRC investigators and resources. These include:

• Critical refinements in defining the clinical course, signs, and symptoms of the disease. ⁵ , ⁶

• Development and validation of reliable diagnostic procedures. ⁷

• Advancement in understanding clinicopathological correlations. ⁸

• Elucidation of major risk factors for ADRD. ⁹

• Identification of the important contribution of cerebrovascular disease and other neurodegenerative diseases to the severity and heterogeneity of cognitive symptoms. ¹⁰ , ¹¹

ADRC  investigators have also made foundational contributions to the genetics and biomarker science that underpin today's diagnostic and therapeutic landscape. These contributions include identifying the apolipoprotein E ε4 (APOE ε4) allele as the most significant inherited risk factor for sporadic AD, ¹² mapping and cloning genes on chromosomes 21, 14, and 1 that cause familial forms of the disease, ¹³ and developing methods to identify genetic contributors to late‐onset AD. ¹⁴ Research on normal aging and preclinical disease stages, much of it pioneered within ADRCs, laid the groundwork for biomarker‐based disease definitions. ¹⁵ ADRC‐supported science also enabled the development of positron emission tomography (PET) imaging agents that detect amyloid beta plaques in vivo, ¹⁶ providing clinicians and researchers with a powerful tool to differentiate AD from other causes of cognitive impairment.

FIGURE 1.

ADRCs and NACC work with SCAN, NCRAD, NIAGADS, and ADGC to share data and samples to investigators everywhere.

One of the more impactful contributions of the ADRC program is the recognition that many more people than previously recognized have mixed dementia, ¹⁷ meaning a combination of two or more neuropathological processes contributing to dementia. In addition to AD, other common forms of dementia include Lewy body dementia, ¹⁸ frontotemporal disorders, ¹⁹ and vascular dementia. ²⁰ A typical example of mixed dementia is the co‐existence of both AD and vascular dementia. Research from ADRCs led to the definition of a new, relatively common form of dementia called limbic‐predominant age‐related TDP‐43 encephalopathy (LATE). ²¹ LATE often mimics the clinical features of Alzheimer's disease, meaning that some people clinically diagnosed with AD may have more LATE pathology than AD pathology. ²² , ²³ ADRC brain bank resources, made possible by the research participants that have graciously agreed to donate their brain at the time of death, are instrumental for empowering the field to develop novel approaches to early detection and treatment across the full range of underlying etiologies that contribute to dementia risk, symptoms, and disease progression.

3. WHAT THE ADRCs PROVIDE

The UDS, collected since 2005, allows data from all ADRCs across the country to be aggregated and curated centrally by the National Alzheimer's Coordinating Center (NACC), the centralized data repository, collaboration, and communication hub for the ADRC program. More than 54,000 participants have UDS data available at NACC, including over 200,000 clinical assessments and 8000 neuropathology exams. Importantly, UDS data from ADRCs are freely available to interested researchers. UDS forms are also used widely in many other studies in the US and internationally, facilitating cross‐study harmonization and substantially increasing the interoperability and scientific value of the datasets. The cognitive status of research volunteers across the ADRCs covers the spectrum, ranging from normal cognition to MCI to dementia.

Neuroimaging is critical for conducting cutting‐edge AD/ADRD research, supporting the validation of other biomarkers, and improving our understanding of the complex interaction of multiple causes of dementia. In addition to uniform clinical and cognitive data collection through UDS, ADRCs now utilize a uniform imaging protocol for prospectively collected PET and magnetic resonance imaging (MRI) images as defined by Standardized Centralized Alzheimer's & Related Dementias Neuroimaging (SCAN), a NIA‐funded project designed to standardize the acquisition, curation, and analysis of ADRC PET and MRI images. The ADRC Consortium for Clarity in ADRD Research Through Imaging (CLARiTI) has further strengthened efforts to support standardized PET, MRI, and plasma biomarker collection across the ADRC program.

Beyond UDS and neuroimaging data, ADRCs also collect biological samples, including plasma, serum, and cerebrospinal fluid, and genetic data, such as APOE genotype and genome‐wide association studies from research participants. Many ADRCs are now also collecting fibroblasts and induced pluripotent stem cell (iPSC) lines that can be differentiated into individual cell types affected in disease, such as neurons, astrocytes, microglia, and oligodendrocytes, as well as three‐dimensional “mini‐brain” organoids. ADRC biosamples are shared locally at each center and through the National Centralized Repository for AD and Related Dementias (NCRAD). The genetic and genomic data are shared through the Alzheimer's Disease Genetics Consortium (ADGC) and the National Institute on Aging Genetics of Alzheimer's Disease Data Storage (NIAGADS). The multimodal ADRC participant data available from NCRAD, NACC, NIAGADS, SCAN, and CLARiTI as well as the AD Knowledge Portal (ADKP) are being integrated longitudinally at the participant level and made discoverable through the NACC Data Front Door (Figure 1). More details about the ADRC‐related data and sample infrastructure programs can be found in Box 1.

BOX 1: Summary of key ADRC data and sample infrastructure programs: NACC, NCRAD, NIAGADS, SCAN, CLARiTI

Resource	Description
National Alzheimer's Coordinating Center (NACC)	The NACC, established in 1999, facilitates collaborative research and standardizes procedures among the ADRCs. NACC serves as the centralized data repository, collaboration, and communication hub for the NIA's ADRC program. NACC developed and maintains a large database of the standardized clinical and neuropathological research data that have been collected from each ADRC. A minimum dataset of 67 variables was collected from the ADRCs since 1984. A much richer longitudinal uniform dataset (UDS, comprising 725 variables) has been collected since 2005. In 2025, the centers implemented a new version, UDS version 4 3 , which includes over 1500 variables and is aligned with the latest scientific advances in the field and our evolving understanding of best clinical practice.
National Centralized Repository for Alzheimer's Disease and Related Dementias (NCRAD)	NIA created the NCRAD in 1990 as the national repository of ADRC participant DNA and cell lines. NIA has substantially expanded NCRAD by increasing the number and types of samples it collects and distributes, as well as adding a biomarker assay laboratory that centralizes and standardizes biomarker assays and enables cross‐laboratory comparability studies. NCRAD collects and shares blood, DNA, cell lines, and other biospecimens from research participants in the ADRCs and other NIA‐funded studies.
National Institute on Aging Genetics of Alzheimer's Disease Data Storage Site (NIAGADS)	The NIAGADS was established in 2012 to ensure that qualified researchers could access the genotypic data generated as part of the NIA's Alzheimer's Disease Genetics Portfolio, including ADRC participants. NIAGADS is hosted at the University of Pennsylvania and works collaboratively with researchers around the world to facilitate access and share genomic and associated omics data related to AD/ADRD as well as healthy aging.
Standardized Centralized Alzheimer's & Related Dementias Neuroimaging (SCAN)	SCAN is a multi‐institutional project, initiated in 2020, that is designed to standardize the acquisition, curation, and analysis of PET and MRI scans acquired through the ADRC program. The NACC data platform enhances the SCAN dataset by linking SCAN images and analysis results with the longitudinal Uniform Data Set and other data modalities and by supporting integrated discovery of SCAN data alongside other ADRC data modalities via the NACC Data Front Door.
ADRC Consortium for Clarity in ADRD Research Through Imaging (CLARiTI)	CLARiTI, established in 2023, collects neuroimaging (PET and MRI) and plasma biomarker data on approximately 2000 AD/ADRD and healthy control participants across all ADRCs.

BOX 2. Summary of ADRC components: Administrative core, Clinical core, Neuropathology core, Outreach, Recruitment and Engagement core, Data Management and Statistical core, Biomarker core, Research Education Component (REC), and Optional cores

Core	Description
Administrative core	Manages and coordinates interactions within the center and with researchers utilizing the center's resources both within and outside of their institution, including across the ADRC network. The administrative core also supports the required developmental project program that provides an opportunity for high‐risk, high‐reward investigations that utilize the unique resources of the ADRC and can lead to independently funded research.
Clinical core	Establishes and maintains a well‐characterized, longitudinal cohort of research participants. The demographics of each center's clinical core cohort reflect the specific theme and research interests of the ADRC. Research participants in the ADRC clinical core contribute data to the NACC database, which now includes more than 204,000 clinical assessments from all ADRCs ever funded.
Neuropathology core	Conducts autopsies, which are offered to all participants. The combined data include over 8300 neuropathology exams involving 58% of deceased participants, just since 2005. This valuable resource has contributed tremendously to research in AD/ADRD and to our understanding of the many different causes of cognitive impairment. 24
Outreach, Recruitment and Engagement core	Provides outreach to the public and facilitates participant recruitment for the ADRC, affiliated studies, and large‐scale national projects, such as the NIA's Genetics Initiative, Alzheimer's Clinical Trials Consortium (ACTC), and Alzheimer's Disease Neuroimaging Initiative (ADNI), as well as for other research and clinical trials. Collaborations include ongoing interactions with local and national governmental and non‐governmental organizations.
Data Management and Statistical core	Supports data management, provides statistical consultation, and ensures data interconnectedness across all cores of the center. In addition to submitting UDS data to NACC, the DMS core ensures that ADRC samples and data are available to interested investigators both within and outside the ADRC.
Biomarker core	Collects, stores, tracks, shares, and analyzes biomarkers (e.g., fluid, image, wearable), which may be standard or novel biomarkers. Contributes to understanding of heterogeneity, onset, or progression of disease symptoms and/or improved diagnosis. Catalogs of available biomarkers and relevant data are made available to researchers outside the ADRC. A dedicated biomarker core was a new requirement with the 2019 funding opportunity. Prior to that, many centers already had an imaging core, genetics core, or other biomarker core.
Research Education Component (REC)	Supports research educational and training activities to develop a multifaceted workforce to meet the nation's research needs in AD/ADRD. This includes increasing expertise and developing the next generation of scientists who will be effective in leading cross‐disciplinary, translational, team‐science projects. Since the formalized REC was introduced in 2016, ADRCs have supported over 1800 AD/ADRD scholars and trainees.
Optional cores	Utilize a center's local expertise to advance some aspect of AD/ADRD research. Among 37 ADRCs, 28 include at least one optional core, and there is a total of 44 optional cores. Although imaging can be included in a biomarker core, 19 centers have both a biomarker core and a separate imaging core. Additionally, six have separate genetics cores (three more have genetics as part of their biomarker core), four have iPSC cores, and 10 have special population cores.

Centers also  support educational activities that complement and enhance the development of a workforce to meet the nation's biomedical, behavioral, and clinical needs in dementia‐related research. There are a wide range of educational activities that provide research experiences to promote the development of future research leaders, particularly leaders who can integrate clinical insights with knowledge of advances in basic and translational sciences to improve interventions for maintaining cognitive health and reducing risk for cognitive impairment.

FIGURE 2.

Current component structure of an ADRC. Further details are provided in Box 1.

In addition to research and training, the ADRCs provide an important resource for people with dementia, their families, and the community. The centers help people obtain diagnoses and medical management. Centers provide information about different types of dementia, services (such as social workers, support groups, and special programs), and resources (such as local chapters of non‐governmental organizations or public health resources) to the community, ensuring that all populations have the opportunity to participate in clinical studies, research registries, and clinical trials.

4. ADRC PROGRAM OVERVIEW AND STRUCTURE

As required by the NIA, ADRCs have a common set of cores, which organizationally enable centers to provide data and samples to researchers, educational resources to the community, and diagnoses to research participants. When the first five ADCs were funded in 1984, they were each mandated to have three cores: Administrative, Clinical, and Neuropathology. As the landscape of AD/ADRD research evolved, new cores and components became a standard part of each center. In addition to the Administrative, Clinical, and Neuropathology cores, all ADRCs are now also required to have the following additional cores and components: the Outreach, Recruitment, and Engagement (ORE) Core, Data Management and Statistical (DMS) Core, Biomarker Core, and Research Education Component (REC). More information about the structure of each ADRC and definitions of the required cores are outlined below (Figure 2 and Box 2).

5. ADRC FUTURE DIRECTIONS

Building on four decades of foundational discoveries and infrastructure, the ADRC program has played a critical role in advancing AD/ADRD research and is now positioned to address emerging scientific questions that require integrated, longitudinal, and multimodal approaches. As the program continues, the ADRCs will collectively work to enhance understanding of the processes and risk factors underlying transitions from normal aging to MCI to full‐blown AD, as well as the overlap and interaction between AD and other neurodegenerative diseases. The centralized and integrated multidisciplinary expertise at each ADRC enables cutting‐edge science, including the integration of digital pathology, multi‐omics, and other innovative cross‐disciplinary approaches. ²⁵ Recent studies, including research from ADRCs, suggest that disease processes common to several conditions often overlap in people with symptoms of dementia. ²⁶ Looking forward, the ADRC program will follow up on these important findings by placing a particular emphasis on understanding the etiology, diagnosis, and treatment of mixed dementias.

The ADRCs play an increasingly critical role in advancing early detection of AD/ADRD through the discovery of new biomarkers and improved approaches to identifying risk factors that predict cognitive decline and support timely diagnosis of cognitive impairment and dementia. Further, the ADRCs will disseminate and utilize clinically valuable data that have been paired with neuroimaging, biospecimens, biomarkers, and neuropathology data. The ADRC program is well positioned to enhance understanding of the risk factors that contribute to differences in health outcomes across populations in the United States and elucidate how these differences are linked to disease processes and disease burden. Importantly, the recently updated UDS version 4 will enable the ADRCs to support evaluation of new AD/ADRD treatments across the centers. ³ As new treatments become available, researchers will be able to examine the impact of current and future FDA‐approved AD/ADRD disease‐modifying treatments on the trajectory and biology of the diseases and on the quality of life of the people and families who are living with neurodegenerative diseases.

CONFLICT OF INTEREST STATEMENT

The authors declare no conflicts of interest. Author disclosures are available in the Supporting Information.

Supporting information

Supporting material: alz71511‐sup‐0001‐Disclosureforms.pdf

Donley G, Hsiao J, Balintfy J, Silverberg N. Four decades of Alzheimer's disease discoveries, data, and research resources: The NIH Alzheimer's Disease Research Center Program. Alzheimer's Dement. 2026;22:e71511. 10.1002/alz.71511