The Dominantly Inherited Alzheimer Network (DIAN) is an international research consortium studying individuals with autosomal dominant [Alzheimer's Disease](/diseases/alzheimers-disease) caused by deterministic genetic mutations in [APP](/genes/app), [PSEN1](/genes/psen1), or [PSEN2](/genes/psen2).[@bateman2012] DIAN provides a unique opportunity to study the preclinical and prodromal stages of AD, as mutation carriers develop the disease at a predictable age.
Study Design
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Introduction
Mermaid diagram (expand to render)
The Dominantly Inherited Alzheimer Network (DIAN) is an international research consortium studying individuals with autosomal dominant [Alzheimer's Disease](/diseases/alzheimers-disease) caused by deterministic genetic mutations in [APP](/genes/app), [PSEN1](/genes/psen1), or [PSEN2](/genes/psen2).[@bateman2012] DIAN provides a unique opportunity to study the preclinical and prodromal stages of AD, as mutation carriers develop the disease at a predictable age.
Study Design
DIAN employs a multi-site, family-based, longitudinal cohort design:[@mcdade2022]
Mutation Carriers: Individuals with pathogenic APP, PSEN1, or PSEN2 mutations
Non-Carriers: Siblings without the mutation (control group)
At-Risk Individuals: Asymptomatic family members with unknown mutation status
The study is specifically designed to capture the presymptomatic stage of AD, with participants enrolled based on their estimated years from onset.
Key Objectives
Biomarker Discovery: Identify the earliest biomarkers of AD before clinical symptoms[@bateman2012]
Disease Timeline: Characterize the sequence of biomarker changes in autosomal dominant AD
Therapeutic Trials: Enable prevention trials in pre-symptomatic individuals[@reiman2019]
Genetic Studies: Understand how different mutations affect disease progression
Data Collection
Genetic Data
Mutation Screening: Genetic testing for APP, PSEN1, and PSEN2 mutations
APOE Genotyping: Analysis of modulatory risk alleles
Clinical Dementia Rating (CDR): Staging of dementia severity
Neurological Examinations: Standardized motor and sensory assessments
Psychiatric Evaluation: Mood and behavioral assessments
Major Findings
Biomarker Timeline
DIAN established the first comprehensive biomarker timeline for autosomal dominant AD, showing that amyloid changes occur 15-25 years before clinical onset, followed by neurodegenerative changes and cognitive decline[@bateman2012]
Amyloid Deposition
The study demonstrated that amyloid deposition follows a predictable pattern, beginning in the precuneus and frontal regions before spreading throughout the brain[@villemagne2013]
Tau Pathology
DIAN has shown that tau PET signal increases approximately 10 years before symptom onset, with a characteristic pattern starting in the temporal lobe[@gordon2018]
Cognitive Decline
Longitudinal cognitive data show that subtle cognitive changes begin 5-10 years before clinical diagnosis, with progressive decline in multiple domains[@lim2017]
Impact on Research
DIAN has significantly advanced the field by:[@reiman2019]
Providing the first detailed biomarker trajectory for preclinical AD
Enabling prevention trials in asymptomatic individuals (DIAN-TU)
Establishing criteria for preclinical AD classification
Validating amyloid and tau PET tracers
Participating Institutions
DIAN involves collaboration among major research centers worldwide:
Washington University in St. Louis (lead site)
University of California, Los Angeles
Columbia University
University of Pittsburgh
University of Melbourne (Australia)
University of Munich (Germany)
Tokyo Metropolitan Institute (Japan)
The study is funded by the National Institute on Aging (NIA) and the Alzheimer's Association.
Data Access
DIAN data are available to qualified researchers:[@diano2024]
Through the DIAN Data Request Portal
The Laboratory of Neuro Imaging (LONI) archive
Collaborative analysis agreements
DIAN-TU Clinical Trials
DIAN includes the DIAN-TU (Trials Unit), which conducts prevention trials in mutation carriers:
Active Trials: Multiple anti-amyloid and anti-tau therapies
Outcome Measures: Cognitive, imaging, and biomarker endpoints
Target Population: Pre-symptomatic and mildly symptomatic carriers