Dominantly Inherited Alzheimer Network (DIAN) (DIAN)

May 12, 2026 updated by: Washington University School of Medicine
The purpose of this study is to identify potential biomarkers that may predict the development of Alzheimer's disease in people who carry an Alzheimer's mutation.

Study Overview

Status

Recruiting

Conditions

Detailed Description

Dominantly inherited Alzheimer's disease (AD) represents less than 1% of all cases of AD and is an important model for study because the responsible mutations have known biochemical consequences that are believed to underlie the pathological basis of the disorder. Three major hypotheses will be tested:

  • First, that there is a period of preclinical (presymptomatic) AD in individuals who are destined to develop early-onset dementia (gene carriers) that can be detected by changes in biological fluids and in neuroimaging correlates in comparison with individuals who will not develop early-onset dementia (non-carriers).
  • Second, because all identified causative mutations for AD affect the normal processing of amyloid precursor protein (APP) and increase brain levels of amyloid-beta 42 (Aβ42), the sequence of preclinical changes initially will involve Aβ42 (production and clearance; reduced levels in cerebrospinal fluid [CSF]), followed by evidence for cerebral deposition of Aβ42 (amyloid imaging), followed by cerebral metabolic activity (functional imaging), and finally by regional atrophy (structural imaging).
  • Finally, that the phenotype of symptomatic early-onset familial AD, including its clinical course, is similar to that of late-onset "sporadic" AD.

The following specific aims will be used to test these hypotheses:

  1. Maintain the established international DIAN registry of individuals (MCs and non-carriers (NC), symptomatic and asymptomatic) who are biological adult children of an affected parent with an APP, PSEN1, or PSEN2 mutation causing AD and assess participants every 2 years with the uniform DIAN protocol.
  2. Recruit to the registry 50 new asymptomatic participants, both MCs and NCs, in Year 1 of the next budget period to maintain the total DIAN cohort at ~250 individuals. These new participants will include those who are more than 15 years younger than the estimated age of symptomatic onset (EAO) to explore the earliest observable biomarker changes of preclinical AD.

  3. Maintain the integrated DIAN database and biospecimen repository to disseminate data and tissue to qualified investigators (within and outside of DIAN) in a user-friendly manner and to permit analyses within, between, and among the various data domains that will include:

    1. In asymptomatic MCs (using NCs as controls), determine the temporal ordering and rate of intraindividual change in clinical, cognitive, imaging, and fluid biomarkers of AD prior to EAO
    2. In symptomatic MCs, compare the clinical and neuropathological phenotypes of ADAD to those of LOAD, using datasets such as ADNI.
  4. Utilize the DIAN cohort and its database and biospecimen repository to support new scientific studies, including use of exome chip technology to examine potential modifiers of age at symptomatic onset. Pursue other new scientific initiatives that are funded independently of the DIAN grant but are conducted within the DIAN infrastructure at no cost to DIAN including: Dermal fibroblasts and induced pluripotent stem cells (iPSCs), examine biomarker surrogates for neurogeneration in CSF including Visinin-like protein-1 (VILIP-1), Tau seeding assay, Stable Isotope Leucine Kinetics (SILK) in DIAN participants, determine the exact Abeta species that underlie AD pathology using Mass spectrometry, exome sequencing on all DIAN participants to search for both positive and negative modifiers of EYO, and amyloid imaging crossover to [18F]florbetapir.
  5. Provide genetic counseling to any and all DIAN participants who wish to learn their mutation status and, for those who decide to learn their status after counseling, provide genetic testing by Clinical Laboratory Improvement Amendments (CLIA)-approved laboratories (i.e., outside of DIAN).

Study Type

Observational

Enrollment (Estimated)

700

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Contact

  • Name: Alisha Daniels, MD,MHA
  • Phone Number: (314) 273-9057

Study Contact Backup

Study Locations

  • Argentina
      • Buenos Aires, Argentina
        • Recruiting
        • Fundación para la Lucha contra las Enfermedades Neurológicas de la Infancia" (FLENI) Instituto de Investigaciones Neurológicas Raúl Correa
        • Contact:
        • Principal Investigator:
          • Ricardo Allegri, MD, PhD
    • Salta Province
      • Salta, Salta Province, Argentina
        • Recruiting
        • Fundación para la Lucha contra las Enfermedades Neurológicas de la Infancia (FLENI)
        • Principal Investigator:
          • Ricardo Allegri, MD, PhD
        • Contact:
  • Australia
    • New South Wales
      • Sydney, New South Wales, Australia, 2031
    • Victoria
      • Melbourne, Victoria, Australia, 3130
        • Suspended
        • Mental Health Research Institute, University of Melbourne
    • Western Australia
      • Perth, Western Australia, Australia, 6009
        • Recruiting
        • Sir James McCusker Alzheimer's Disease Research Unit, Edith Cowan University
        • Contact:
        • Principal Investigator:
          • Ralph Martins, PhD
        • Contact:
  • Brazil
    • São Paulo
      • São Paulo, São Paulo, Brazil, 05403-900
        • Recruiting
        • Hospital das Clínicas da Faculdade de Medicina da Universidade de Sao Paulo
        • Principal Investigator:
          • Leonel Tadao Takada, MD, PHD
        • Contact:
        • Contact:
  • Canada
    • Quebec
      • Verdun, Quebec, Canada, H4H 1R3
        • Not yet recruiting
        • McGill University Research Centre for Studies in Aging
        • Contact:
        • Principal Investigator:
          • Pedro Rosa-Neto, MD,PhD
  • Colombia
    • Colombia
      • Medellín, Colombia, Colombia
        • Recruiting
        • Grupo Neurociencias de Antioquia
        • Contact:
        • Principal Investigator:
          • David Aguillon, MD
  • Germany
      • Munich, Germany, D-81377
        • Recruiting
        • German Center for Neurodegenerative Diseases (DZNE) Munich, and University Hospital Ludwig-Maximilians-Universitat (LMU) Munich
        • Principal Investigator:
          • Johannes Levin, MD, PhD
        • Contact:
      • Tübingen, Germany, D-72076
        • Recruiting
        • German Center for Neurodegenerative Diseases (DZNE) Tübingen and Hertie-Institute for Clinical Brain Research, University of Tübingen
        • Principal Investigator:
          • Mathias Jucker, PhD
        • Contact:
  • Japan
  • Mexico
    • Mexico City
      • Mexico City, Mexico City, Mexico, 14269
        • Recruiting
        • Instituto Nacional de Neurología y Neurocirugía "Manuel Velasco Suarez"
        • Contact:
        • Principal Investigator:
          • Ana Luisa Sosa Ortiz, PHD
        • Sub-Investigator:
          • Erika Mariana Longoria Ibarrola, MD
  • Netherlands
      • Amsterdam, Netherlands, 1081HV
        • Recruiting
        • Amsterdam UMC
        • Contact:
        • Principal Investigator:
          • Lisa Vermunt, MD,PhD
  • South Korea
    • Songpa-Gu
      • Seoul, Songpa-Gu, South Korea, 05505
        • Recruiting
        • Asan Medical Center
        • Contact:
        • Principal Investigator:
          • Jae Hong Lee, MD, PhD
  • Spain
    • Catalonia
      • Barcelona, Catalonia, Spain, 08036
        • Suspended
        • Hospital Clinic Barcelona
  • United Kingdom
      • London, United Kingdom, WC1N 3BG
        • Recruiting
        • Institute of Neurology, Queen Square
        • Contact:
        • Principal Investigator:
          • Nick Fox, MD
  • United States
    • Florida
      • Jacksonville, Florida, United States, 32224
    • Indiana
      • Indianapolis, Indiana, United States, 46202
        • Recruiting
        • Indiana University-Indiana Alzheimer Disease Center
        • Contact:
        • Principal Investigator:
          • Martin Farlow, MD
    • Massachusetts
      • Boston, Massachusetts, United States, 02115
    • Missouri
      • St Louis, Missouri, United States, 63108
        • Recruiting
        • Washington University in St. Louis School of Medicine
        • Principal Investigator:
          • Randall Bateman, MD
        • Contact:
        • Contact:
    • New York
      • New York, New York, United States, 10032
        • Suspended
        • Columbia University
    • Pennsylvania
      • Pittsburgh, Pennsylvania, United States, 15260
        • Recruiting
        • University of Pittsburgh
        • Contact:
        • Principal Investigator:
          • Sarah Berman, MD, PhD
    • Rhode Island
      • Providence, Rhode Island, United States, 02906
        • Recruiting
        • Butler Hospital
        • Principal Investigator:
          • Edward Huey, MD
        • Contact:
    • Washington
      • Seattle, Washington, United States, 98195
        • Recruiting
        • University of Washington
        • Contact:
        • Principal Investigator:
          • Suman Jayadev, MD
        • Contact:

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

18 years and older (Adult, Older Adult)

Accepts Healthy Volunteers

Yes

Sampling Method

Non-Probability Sample

Study Population

Mutation carriers and non-carriers from families with a mutation (which is different from the genetic risk factor Apo-E4) known to cause Alzheimer's disease.

Description

Inclusion Criteria:

  • Written informed consent obtained from participant and collateral source prior to any study-related procedures.
  • Aged 18 (inclusive) or older and the child of an affected individual (clinically or by testing) in a pedigree with a known mutation for ADAD.
  • Cognitively normal to very mild or mild cognitive impairment (CDR score range 0-1.0). Primary enrollment will focus on the recruitment of asymptomatic adult children who are more than 15 years younger than the estimated age of symptom onset. Enrollment of new participants with moderate cognitive impairment is allowed with the prior approval of the DIAN Coordinating Center.
  • Has two persons who are not their full-blooded siblings who can serve as collateral sources for the study.
  • Fluent in a language approved by the DIAN Coordinating Center at about the 6th grade level (international equivalent) or above.

Exclusion Criteria:

  • Under age 18
  • Medical or psychiatric illness that would interfere in completing initial and follow-up visits
  • Requires nursing home level care
  • Has no one who can serve as a study informant

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Observational Models: Cohort
  • Time Perspectives: Prospective

Cohorts and Interventions

Group / Cohort
1
Mutation Positive
2
Mutation Negative

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Time Frame
Positive predictive power of a biomarker or group of biomarkers
Time Frame: Variable follow-up assessment based on age in relation to age at onset of affected parent.
Variable follow-up assessment based on age in relation to age at onset of affected parent.
Biomarkers obtained by blood draw, lumbar puncture, MRI, FDG PET, PET amyloid imaging
Time Frame: Variable follow-up assessment based on age in relation to age at onset of affected parent
Variable follow-up assessment based on age in relation to age at onset of affected parent
Clinical markers also examined from clinical interview and cognitive testing
Time Frame: Variable follow-up assessment based on age in relation to age at onset of affected parent
Variable follow-up assessment based on age in relation to age at onset of affected parent

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Washington University School of Medicine

Collaborators

National Institute on Aging (NIA)

Investigators

  • Study Director: Alisha Daniels, MD,MHA, (314) 273-9057
  • Principal Investigator: Eric McDade, DO, Washington University School of Medicine

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Helpful Links

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start

January 1, 2009

Primary Completion (Estimated)

July 1, 2026

Study Completion (Estimated)

July 1, 2026

Study Registration Dates

First Submitted

March 25, 2009

First Submitted That Met QC Criteria

March 25, 2009

First Posted (Estimated)

March 26, 2009

Study Record Updates

Last Update Posted (Actual)

May 15, 2026

Last Update Submitted That Met QC Criteria

May 12, 2026

Last Verified

May 1, 2026

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • IA0147
  • U19AG032438 (U.S. NIH Grant/Contract)

Drug and device information, study documents

product manufactured in and exported from the U.S.

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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