Dominantly Inherited Alzheimer Network (DIAN)



Status:Recruiting
Conditions:Alzheimer Disease
Therapuetic Areas:Neurology
Healthy:No
Age Range:18 - Any
Updated:9/30/2017
Start Date:January 2009
End Date:June 2019
Contact:DIAN Global Coordinator
Phone:314-747-1940

Use our guide to learn which trials are right for you!

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.

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 (mutation carriers
and non-carriers; pre-symptomatic and symptomatic) who are biological adult children of
a parent with a known causative mutation for AD in the APP, PSEN1, or PSEN2 genes and
assess participants every 2 years with the uniform DIAN protocol.

2. 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 mutation carriers (using non-carriers as controls), determine the
temporal ordering and rate of intraindividual change in clinical, cognitive,
behavioral, imaging, and fluid biomarkers of AD prior to estimated age of symptom
onset.

2. In symptomatic mutation carriers, compare the clinical and neuropathological
phenotypes of ADAD to those of LOAD, using datasets such as ADNI.

3. 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, exploratory investigation of new biomarker
analytes, imaging modalities and techniques, perform exploratory genetic analysis to
test whether novel AD genes identified through GWAS and sequencing of late onset AD
cases also influence variation in age at onset of changes in biomarker endophenotypes in
FAD kindred, and generate genome-wide DNA methylation data for pilot study and perform
exploratory analyses to look for changes in DNA methylation in longitudinal samples from
DIAN participants.

4. 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).

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. Primary enrollment will focus on recruitment of asymptomatic adult
children who are more than 15 years younger than the estimated age of symptom onset.
Enrollment of new participants with very mild, mild, or 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
We found this trial at
9
sites
Los Angeles, California 90033
213) 740-2311
Principal Investigator: Helena Chui, MD
Phone: 323-442-2357
University of Southern California The University of Southern California is one of the world’s leading...
?
mi
from
Los Angeles, CA
Click here to add this to my saved trials
75 Francis street
Boston, Massachusetts 02115
(617) 732-5500
Principal Investigator: Jasmeer Chhatwal, MD, PhD
Phone: 617-643-7799
Brigham and Women's Hosp Boston’s Brigham and Women’s Hospital (BWH) is an international leader in...
?
mi
from
Boston, MA
Click here to add this to my saved trials
116th St and Broadway
New York, New York 10027
(212) 854-1754
Principal Investigator: James Noble, MD
Phone: 212-305-5909
Columbia University In 1897, the university moved from Forty-ninth Street and Madison Avenue, where it...
?
mi
from
New York, NY
Click here to add this to my saved trials
4200 Fifth Ave
Pittsburgh, Pennsylvania 15260
(412) 624-4141
Principal Investigator: Sarah Berman, MD, PhD
Phone: 412-692-2740
University of Pittsburgh The University of Pittsburgh is a state-related research university, founded as the...
?
mi
from
Pittsburgh, PA
Click here to add this to my saved trials
?
mi
from
Buenos Aires,
Click here to add this to my saved trials
Indianapolis, Indiana 46202
Principal Investigator: Bernardino Ghetti, MD
Phone: 317-963-1847
?
mi
from
Indianapolis, IN
Click here to add this to my saved trials
Jacksonville, Florida 32216
Principal Investigator: Neil R. Graff-Radford, MD
Phone: 904-953-3234
?
mi
from
Jacksonville, FL
Click here to add this to my saved trials
345 Blackstone Blvd
Providence, Rhode Island 02906
(401) 455-6200
Principal Investigator: Stephen Salloway, MD
Phone: 401-455-6403
Butler Hospital Founded in 1844, Butler Hospital is the state's only non-profit, free-standing psychiatric hospital...
?
mi
from
Providence, RI
Click here to add this to my saved trials
660 S Euclid Ave
Saint Louis, Missouri 63110
(314) 362-5000
Principal Investigator: Randall Bateman, MD
Phone: 314-362-2256
Washington University School of Medicine Washington University Physicians is the clinical practice of the School...
?
mi
from
Saint Louis, MO
Click here to add this to my saved trials