Alzheimer's DiseaseDIANNCT00869817
Dominantly Inherited Alzheimer Network (DIAN)
An observational study of Alzheimer's Disease, run by Washington University School of Medicine at 26 sites in 13 countries.
Trial summary
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. Read more about this study
- Who is it for?
- Ages 18 years and olderHealthy volunteers can take part
- Conditions the study is for
- Alzheimer's Disease
- How many people
- 700 participants
- Where
- 26 sitesin 13 countries
- Study dates
- Jan 2009to Sep 2031
- Phase
- Observational
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- Healthy volunteers accepted
- Adult, Older adult
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.
Who may be able to join
- 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.
Who cannot join
- 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
Trial locations and contacts
26 sites in 13 countries. Contact the study team or a site near you to ask about taking part.
Alisha Daniels, MD,MHA contact
DIAN Obs Admin Core contact
26 sites in 13 countries
United States8 sites, 7 recruiting
- Recruiting
Brigham and Women's Hospital
Boston, Massachusetts, 02115
Alexa Coussoule, acoussoule@bwh.harvard.edu
Paola Matos, pmatos1@mgh.harvard.edu
- Recruiting
Indiana University-Indiana Alzheimer Disease Center
Indianapolis, Indiana, 46202
Jill Buck, RN, 317-963-1847, jilmbuck@iu.edu
Martin Farlow, MD
- Recruiting
Mayo Clinic Jacksonville
Jacksonville, Florida, 32224
Ercilia Moncayo, Moncayo.Ercilia@mayo.edu
Twila Morrell, BS, Morrell.Twila@mayo.edu
- Suspended
Columbia University
New York, New York, 10032
- Recruiting
University of Pittsburgh
Pittsburgh, Pennsylvania, 15260
Zana Ikonomovic, MD, 412-692-2740, ikonomovics@upmc.edu
Sarah Berman, MD, PhD
- Recruiting
Butler Hospital
Providence, Rhode Island, 02906
Courtney Bodge, PhD, (401) 455-6403, cbodge@butler.org
Edward Huey, MD
- Recruiting
University of Washington
Seattle, Washington, 98195
Sarah Taylor, saraht73@uw.edu
Emmaline Seth, emmaseth@uw.edu
- Recruiting
Washington University in St. Louis School of Medicine
St Louis, Missouri, 63108
McCrae Johnson, RN, MSN, mccrae@wustl.edu
Georgia Stobbs-Cucchi, RN, gstobbs@wustl.edu
Australia3 sites, 2 recruiting
- Suspended
Mental Health Research Institute, University of Melbourne
Melbourne, Victoria, 3130
- Recruiting
Sir James McCusker Alzheimer's Disease Research Unit, Edith Cowan University
Perth, Western Australia, 6009
Kevin Taddei, +61-(0)8-6304-5107, k.taddei@ecu.edu.au
Samantha Gardener, s.gardener@ecu.edu.au
- Recruiting
Neuroscience Research Australia
Sydney, New South Wales, 2031
Jacob Bechara, j.bechara@neura.edu.au
William Brooks, MBBS, MPH, w.brooks@NeuRA.edu.au
Japan3 sites, 2 recruiting
- Recruiting
Niigata University
Niigata
Sumie Tsuruki, sumietsuruki@bri.niigata-u.ac.jp
Maki Watanabe, m-watanabe@iris-aumn.co.jp
- Suspended
Osaka City University
Osaka
- Recruiting
Tokyo University
Tokyo
Haruko Kuzuyamah, kuzuyamah@g.ecc.u-tokyo.ac.jp
Yoshiki Niimi, MD
Argentina2 sites, 2 recruiting
- Recruiting
Fundación para la Lucha contra las Enfermedades Neurológicas de la Infancia" (FLENI) Instituto de Investigaciones Neurológicas Raúl Correa
Buenos Aires
Patricio Chrem, MD, 20565342, pchremmendez@fleni.org.ar
Ricardo Allegri, MD, PhD
- Recruiting
Fundación para la Lucha contra las Enfermedades Neurológicas de la Infancia (FLENI)
Salta, Salta Province
Patricio Chrem, pchremmendez@fleni.org.ar
Ricardo Allegri, MD, PhD
Germany2 sites, 2 recruiting
- Recruiting
German Center for Neurodegenerative Diseases (DZNE) Munich, and University Hospital Ludwig-Maximilians-Universitat (LMU) Munich
Munich, D-81377
Ilona Ruge, Ilona.Ruge@dzne.de
Johannes Levin, MD, PhD
- Recruiting
German Center for Neurodegenerative Diseases (DZNE) Tübingen and Hertie-Institute for Clinical Brain Research, University of Tübingen
Tübingen, D-72076
Beatrice Spring, beatrice.spring@med.uni-tuebingen.de
Mathias Jucker, PhD
Brazil1 site, 1 recruiting
- Recruiting
Hospital das Clinicas da Faculdade de Medicina da Universidade de São Paulo
São Paulo, São Paulo, 05403-900
Aline Nishizawa, anishizawa1@gmail.com
Carreira Luzia Lima, luzia.carreira@hc.fm.usp.br
Canada1 site, 1 recruiting
- Not yet recruiting
McGill University Research Centre for Studies in Aging
Verdun, Quebec, H4H 1R3
Tamar Tatigian, tamar.tatigian@mcgill.ca
Pedro Rosa-Neto, MD,PhD
Colombia1 site, 1 recruiting
- Recruiting
Grupo Neurociencias de Antioquia
Medellín, Colombia
Yudy Milena León Varela, yudy.leon@gna.org.co
David Aguillon, MD
Mexico1 site, 1 recruiting
- Recruiting
Instituto Nacional de Neurología y Neurocirugía "Manuel Velasco Suarez"
Mexico City, Mexico City, 14269
Gabriela Rojas de la Torre, MS, MA, gabriella.delatorre.1066@gmail.com
Ana Luisa Sosa Ortiz, PHD
Netherlands1 site, 1 recruiting
- Recruiting
Amsterdam UMC
Amsterdam, 1081HV
Bram Bongers, b.bongers@amsterdamumc.nl
Lisa Vermunt, MD,PhD
South Korea1 site, 1 recruiting
- Recruiting
Asan Medical Center
Seoul, Songpa-Gu, 05505
Jee Hoon Roh, MD, PhD, 82-2-3010-3443, roh@amc.seoul.kr
Jae Hong Lee, MD, PhD
United Kingdom1 site, 1 recruiting
- Recruiting
Institute of Neurology, Queen Square
London, WC1N 3BG
Helen Rice, RN, 07741 671 840, helen.rice2@nhs.net
Nick Fox, MD
About this study
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.
Read the 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:
- 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.
- 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.
- 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:
- 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
- In symptomatic MCs, compare the clinical and neuropathological phenotypes of ADAD to those of LOAD, using datasets such as ADNI.
- 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.
- 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).
- Conditions
- Alzheimer's Disease
- Keywords
- Alzheimer's disease, antecedent biomarkers, Amyloid Precursor Protein (APP) mutation, presenilin I (PS1) mutation, presenilin 2 (PS2) mutation, Autosomal Dominant Alzheimer's Disease
- Medical subject headings
- Alzheimer Disease, Alzheimer disease, familial, type 3, Alzheimer disease type 4
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
| Study group | Role | What they receive |
|---|---|---|
| 1 | Mutation Positive | |
| 2 | Mutation Negative |
What is being measured
The primary outcome is the main question the study is designed to answer.
Positive predictive power of a biomarker or group of biomarkers
Measured: 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
Measured: 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
Measured: Variable follow-up assessment based on age in relation to age at onset of affected parent
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted26 Mar 2009 (estimated)
- Study startJan 2009
- Primary completionSep 2031 (estimated)
- Study completionSep 2031 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (9)Papers the sponsor has linked to this study.
- Other trials for Alzheimer's DiseaseStudies of the same condition, open and under way.
- More trials run by Washington University School of MedicineThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Observational
- Observational model
- Cohort
- Time perspective
- Prospective
- Enrolment
- 700 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Washington University School of Medicine
- Sponsor type
- University, hospital or other
- Collaborators
- National Institute on Aging (NIA)
- Responsible party
- Sponsor
- Investigators
- Eric McDade, DO, Principal investigator, Washington University School of MedicineAlisha Daniels, MD,MHA, Study director, (314) 273-9057
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT00869817
- Sponsor's protocol ID
- IA0147
- Other IDs
- U19AG102728
- Acronym
- DIAN
- Status last verified
- Sep 2026
- First submitted
- 25 Mar 2009
- Last updated
- 5 Oct 2026
- Results posted
- No
- Data monitoring committee
- Yes
Publications
Mintun MA, Larossa GN, Sheline YI, Dence CS, Lee SY, Mach RH, Klunk WE, Mathis CA, DeKosky ST, Morris JC. [11C]PIB in a nondemented population: potential antecedent marker of Alzheimer disease. Neurology. 2006 Aug 8;67(3):446-52. doi: 10.1212/01.wnl.0000228230.26044.a4.
PubMed 16894106Fagan AM, Roe CM, Xiong C, Mintun MA, Morris JC, Holtzman DM. Cerebrospinal fluid tau/beta-amyloid(42) ratio as a prediction of cognitive decline in nondemented older adults. Arch Neurol. 2007 Mar;64(3):343-9. doi: 10.1001/archneur.64.3.noc60123. Epub 2007 Jan 8.
PubMed 17210801Godbolt AK, Cipolotti L, Anderson VM, Archer H, Janssen JC, Price S, Rossor MN, Fox NC. A decade of pre-diagnostic assessment in a case of familial Alzheimer's disease: tracking progression from asymptomatic to MCI and dementia. Neurocase. 2005 Feb;11(1):56-64. doi: 10.1080/13554790490896866.
PubMed 15804925Morris JC, McKeel DW Jr, Storandt M, Rubin EH, Price JL, Grant EA, Ball MJ, Berg L. Very mild Alzheimer's disease: informant-based clinical, psychometric, and pathologic distinction from normal aging. Neurology. 1991 Apr;41(4):469-78. doi: 10.1212/wnl.41.4.469.
PubMed 2011242Galvin JE, Powlishta KK, Wilkins K, McKeel DW Jr, Xiong C, Grant E, Storandt M, Morris JC. Predictors of preclinical Alzheimer disease and dementia: a clinicopathologic study. Arch Neurol. 2005 May;62(5):758-65. doi: 10.1001/archneur.62.5.758.
PubMed 15883263Wagemann O, Li Y, Hassenstab J, Aschenbrenner AJ, McKay NS, Gordon BA, Benzinger TLS, Xiong C, Cruchaga C, Renton AE, Perrin RJ, Berman SB, Chhatwal JP, Farlow MR, Day GS, Ikeuchi T, Jucker M, Lopera F, Mori H, Noble JM, Sanchez-Valle R, Schofield PR, Morris JC, Daniels A, Levin J, Bateman RJ, McDade E, Llibre-Guerra JJ; Dominantly Inherited Alzheimer Network. Investigation of sex differences in mutation carriers of the Dominantly Inherited Alzheimer Network. Alzheimers Dement. 2024 Jan;20(1):47-62. doi: 10.1002/alz.13460. Epub 2023 Sep 23.
PubMed 37740921Prescott JW, Doraiswamy PM, Gamberger D, Benzinger T, Petrella JR; Dominantly Inherited Alzheimer Network. Diffusion Tensor MRI Structural Connectivity and PET Amyloid Burden in Preclinical Autosomal Dominant Alzheimer Disease: The DIAN Cohort. Radiology. 2022 Jan;302(1):143-150. doi: 10.1148/radiol.2021210383. Epub 2021 Oct 12.
PubMed 34636637Gordon BA, Blazey TM, Su Y, Hari-Raj A, Dincer A, Flores S, Christensen J, McDade E, Wang G, Xiong C, Cairns NJ, Hassenstab J, Marcus DS, Fagan AM, Jack CR Jr, Hornbeck RC, Paumier KL, Ances BM, Berman SB, Brickman AM, Cash DM, Chhatwal JP, Correia S, Forster S, Fox NC, Graff-Radford NR, la Fougere C, Levin J, Masters CL, Rossor MN, Salloway S, Saykin AJ, Schofield PR, Thompson PM, Weiner MM, Holtzman DM, Raichle ME, Morris JC, Bateman RJ, Benzinger TLS. Spatial patterns of neuroimaging biomarker change in individuals from families with autosomal dominant Alzheimer's disease: a longitudinal study. Lancet Neurol. 2018 Mar;17(3):241-250. doi: 10.1016/S1474-4422(18)30028-0. Epub 2018 Feb 1.
PubMed 29397305Bateman RJ, Xiong C, Benzinger TL, Fagan AM, Goate A, Fox NC, Marcus DS, Cairns NJ, Xie X, Blazey TM, Holtzman DM, Santacruz A, Buckles V, Oliver A, Moulder K, Aisen PS, Ghetti B, Klunk WE, McDade E, Martins RN, Masters CL, Mayeux R, Ringman JM, Rossor MN, Schofield PR, Sperling RA, Salloway S, Morris JC; Dominantly Inherited Alzheimer Network. Clinical and biomarker changes in dominantly inherited Alzheimer's disease. N Engl J Med. 2012 Aug 30;367(9):795-804. doi: 10.1056/NEJMoa1202753. Epub 2012 Jul 11.
PubMed 22784036