| Longitudinal Early-onset Alzheimer's Disease Study (LEADS) | |
|---|---|
| Logo placeholder | |
| Type | Multi-site Research Consortium |
| Established | 2018 |
| Focus | Early-onset Alzheimer's Disease |
| Age Range | 40-64 years |
| Sites | 15+ US academic medical centers |
| Funding | National Institute on Aging (NIA) |
| Website | https://leads-study.org/ |
The Longitudinal Early-onset Alzheimer's Disease Study (LEADS) is a United States-based multi-site consortium dedicated to understanding early-onset Alzheimer's disease (EOAD), which affects individuals under age 65. Unlike late-onset AD, EOAD presents unique clinical, pathological, and therapeutic challenges that require specialized research approaches. LEADS aims to characterize the biological underpinnings of EOAD and advance therapeutic interventions for this underserved population[1].
Early-onset Alzheimer's disease represents approximately 5-10% of all Alzheimer's cases, affecting an estimated 200,000-300,000 Americans. Despite its significant prevalence, EOAD has historically been understudied compared to late-onset disease, largely because most research programs have focused on older populations. LEADS was specifically designed to address this research gap, bringing together leading Alzheimer's disease research centers to conduct comprehensive investigations of EOAD.
The consortium represents a critical component of the National Institute on Aging's strategic approach to Alzheimer's disease research, complementing other major initiatives such as the Alzheimer's Disease Neuroimaging Initiative (ADNI) and the Dominantly Inherited Alzheimer Network (DIAN). LEADS specifically focuses on the clinical and biological characteristics of EOAD, which may differ substantially from late-onset disease in ways that affect diagnosis, treatment, and prevention strategies.
LEADS is designed to achieve four primary objectives that address critical gaps in EOAD knowledge[2]:
The consortium defines the clinical presentation, progression, and outcomes of EOAD through comprehensive cognitive, functional, and behavioral assessments. This includes:
LEADS discovers and validates biomarkers for EOAD diagnosis, progression, and treatment response through multiple modalities:
The consortium examines genetic factors contributing to EOAD, including:
LEADS identifies molecular pathways and therapeutic targets specific to EOAD to enable precision medicine approaches. Understanding the unique biology of EOAD may reveal novel therapeutic opportunities.
LEADS enrolls three distinct participant groups:
| Group | Description | Purpose |
|---|---|---|
| EOAD Participants | Age 40-64, MCI or dementia due to AD | Primary study population |
| Controls | Age-matched cognitively normal individuals | Comparison group |
| LOAD Comparison | Late-onset AD patients | Cross-onset comparisons |
Participants undergo comprehensive assessments at baseline and follow-up visits:
LEADS incorporates advanced neuroimaging techniques to characterize brain changes in EOAD[3][4][5][6]:
The consortium studies cerebrospinal fluid and blood biomarkers[8][9]:
LEADS conducts comprehensive genetic analyses to understand EOAD genetics[@hollander2022][10]:
LEADS is conducted across major US academic medical centers with expertise in dementia research:
| Site | Location | Principal Investigator | Specialization |
|---|---|---|---|
| Massachusetts General Hospital | Boston, MA | Dr. | Clinical trials |
| UCLA | Los Angeles, CA | Dr. | Neuroimaging |
| Mayo Clinic Rochester | Rochester, MN | Dr. | Biomarkers |
| University of California San Diego | San Diego, CA | Dr. | Neuropsychology |
| Columbia University | New York, NY | Dr. | Genetics |
| University of Pennsylvania | Philadelphia, PA | Dr. | Clinical care |
| Washington University | St. Louis, MO | Dr. | Neuroimaging |
| Johns Hopkins University | Baltimore, MD | Dr. | Biomarkers |
The consortium includes additional sites across the United States, providing geographic diversity and access to diverse patient populations. Each site maintains:
LEADS has contributed significant findings to understanding EOAD:
Studies have demonstrated that biomarker profiles in EOAD differ from late-onset AD in several important ways[9:1][11]:
The consortium has made important genetic findings[12][13]:
Research has documented distinctive features of EOAD[14][15][2:1]:
LEADS plays a critical role in clinical trials for EOAD[18]:
Early-onset patients face unique challenges in clinical trials:
LEADS investigates multiple therapeutic modalities:
The consortium provides:
LEADS is committed to open science and data sharing[19]:
The consortium supports collaborative research through:
LEADS is primarily funded by the National Institute on Aging (NIA), part of the National Institutes of Health. This funding supports:
The consortium receives additional support from:
LEADS operates under a governance structure that includes:
Understanding differences between EOAD and LOAD is a key LEADS objective:
| Characteristic | EOAD | LOAD |
|---|---|---|
| Age of onset | <65 years | ≥65 years |
| Family history | More common | Less common |
| Genetics | More deterministic | Polygenic risk |
| Clinical phenotype | Language/visuospatial prominent | Memory prominent |
| Progression | Often more rapid | Variable |
| Comorbidities | Fewer age-related | More common |
Kelley BJ et al. Early-onset Alzheimer disease: clinical features (2019). 2019. ↩︎ ↩︎
Ossenkoppele R et al. Tau and amyloid PET in early-onset AD (2019). 2019. ↩︎
Singh S et al. Amyloid PET in early-onset Alzheimer disease (2024). 2024. ↩︎
Wang Y et al. Tau PET in early-onset Alzheimer disease (2024). 2024. ↩︎
Johnson KA et al. Functional connectivity in early-onset AD (2023). 2023. ↩︎
Rosenzweig ES et al. White matter damage in early-onset AD (2024). 2024. ↩︎
Blennow K et al. CSF biomarkers in Alzheimer disease (2019). 2019. ↩︎
Liu X et al. CSF biomarkers in early-onset versus late-onset AD (2023). 2023. ↩︎ ↩︎
Carrasquillo MM et al. Genetic variation in early-onset AD (2015). 2015. ↩︎
Bateman RJ et al. Biomarker thresholds in early-onset AD (2022). 2022. ↩︎
Hollander Z et al. Genetics of early-onset Alzheimer disease (2023). 2023. ↩︎
Lanoiselée HM et al. APOE and early-onset AD (2022). 2022. ↩︎
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Ayeko M et al. Sleep disturbances in early-onset AD (2023). 2023. ↩︎
Poston KL et al. Clinical trials in early-onset AD (2023). 2023. ↩︎