The Longitudinal Early-onset Alzheimer's Disease Study (LEADS): Framework and methodology

Alzheimers Dement. 2021 Dec;17(12):2043-2055. doi: 10.1002/alz.12350. Epub 2021 May 21.


Patients with early-onset Alzheimer's disease (EOAD) are commonly excluded from large-scale observational and therapeutic studies due to their young age, atypical presentation, or absence of pathogenic mutations. The goals of the Longitudinal EOAD Study (LEADS) are to (1) define the clinical, imaging, and fluid biomarker characteristics of EOAD; (2) develop sensitive cognitive and biomarker measures for future clinical and research use; and (3) establish a trial-ready network. LEADS will follow 400 amyloid beta (Aβ)-positive EOAD, 200 Aβ-negative EOnonAD that meet National Institute on Aging-Alzheimer's Association (NIA-AA) criteria for mild cognitive impairment (MCI) or AD dementia, and 100 age-matched controls. Participants will undergo clinical and cognitive assessments, magnetic resonance imaging (MRI), [18 F]Florbetaben and [18 F]Flortaucipir positron emission tomography (PET), lumbar puncture, and blood draw for DNA, RNA, plasma, serum and peripheral blood mononuclear cells, and post-mortem assessment. To develop more effective AD treatments, scientists need to understand the genetic, biological, and clinical processes involved in EOAD. LEADS will develop a public resource that will enable future planning and implementation of EOAD clinical trials.

Keywords: Alzheimer's disease; EOAD; LEADS; YOAD; early-onset; young onset.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Alzheimer Disease* / genetics
  • Alzheimer Disease* / pathology
  • Aniline Compounds
  • Autopsy
  • Biomarkers* / blood
  • Biomarkers* / cerebrospinal fluid
  • Biomarkers* / metabolism
  • Brain* / diagnostic imaging
  • Brain* / pathology
  • Cognitive Dysfunction / genetics
  • Cognitive Dysfunction / pathology
  • Early Diagnosis*
  • Female
  • Humans
  • Longitudinal Studies
  • Magnetic Resonance Imaging
  • Male
  • Middle Aged
  • National Institute on Aging (U.S.)
  • Positron-Emission Tomography
  • Stilbenes
  • United States


  • Aniline Compounds
  • Biomarkers
  • Stilbenes
  • 4-(N-methylamino)-4'-(2-(2-(2-fluoroethoxy)ethoxy)ethoxy)stilbene