Dominantly Inherited Alzheimer Network (Dian) is an important component in the neurobiology of neurodegenerative diseases. This page provides detailed information about its structure, function, and role in disease processes.
The Dominantly Inherited Alzheimer Network (DIAN) is an international research consortium established to study individuals with autosomal dominant Alzheimer's Disease (AD), a rare [1]
form of Alzheimer's caused by deterministic genetic mutations.[2] These individuals carry mutations in APP, PSEN1, or PSEN2 that virtually guarantee [3]
development of Alzheimer's Disease.[1:1] [4]
DIAN enrolls three groups: [5]
Participants undergo comprehensive assessments at regular intervals: [6]
Amyloid precursor protein (APP mutations account for approximately 10-15% of AD cases and typically lead to early-onset AD.[10] [4:3]
Presenilin-1 (PSEN1) mutations are the most common cause of AD, representing approximately 70-80% of cases.[11] [5:3]
Presenilin-2 (PSEN2) mutations are rare (5-10% of AD) and often have later onset and more variable presentation.[12] [6:3]
DIAN has demonstrated that amyloid deposition begins approximately 20-25 years before expected symptom onset.[13] This provides a critical window for preventive interventions. [7:1]
Tau pathology and neurodegeneration emerge approximately 10-15 years before symptoms, following amyloid accumulation.[14] [8:1]
Cognitive measures become abnormal approximately 5-10 years before clinical onset.[15] [9:1]
DIAN has established a model of AD pathogenesis: [10:1]
The DIAN Trials Unit (DIAN-TU) conducts therapeutic trials in preclinical AD: [11:1]
DIAN-TU has demonstrated that: [12:1]
DIAN involves over 25 research sites across North America, Europe, Australia, and Asia, coordinated by Washington University School of Medicine in St. Louis. [13:1]
DIAN data are shared with qualified researchers through the DIAN External Science Platform and the Alzheimer's Disease Data Initiative.[27] [14:1]
DIAN has significantly advanced understanding of Alzheimer's Disease: [15:1]
The study of Dominantly Inherited Alzheimer Network (Dian) has evolved significantly over the past decades. Research in this area has revealed important insights into the underlying mechanisms of neurodegeneration and continues to drive therapeutic development. [16:1]
Historical context and key discoveries in this field have shaped our current understanding and will continue to guide future research directions. [17:1]
Additional evidence sources: [18:1] [19:1] [20:1] [21:1] [22:1] [23:1] [24:1] [25:1] [26:1] [27:1] [28:1] [29:1] [30:1] [31:1]
The DIAN-Observational (DIAN-O) study is the foundational component of the DIAN network, enrolling individuals at risk for autosomal dominant Alzheimer's disease (ADAD) due to PSEN1, PSEN2, or APP mutations[1]. Unlike clinical trials, DIAN-O collects comprehensive longitudinal data to characterize the preclinical and prodromal stages of ADAD.
DIAN-O follows a cohort of mutation carriers and non-carriers from families with known ADAD-causing mutations. Participants undergo:
DIAN-O has established the timeline of biomarker changes in preclinical ADAD:
| Biomarker | Years Before Onset |
|---|---|
| CSF Aβ42 decline | 22-25 years |
| Amyloid PET positivity | 15-20 years |
| CSF tau elevation | 10-15 years |
| Hippocampal atrophy | 5-10 years |
| Cognitive impairment | 3-5 years |
This biomarker cascade provides critical insights for prevention trial design[2].
The expanded DIAN-O2 cohort includes additional international sites and enhanced biomarker assessments[3].
Biomarker timeline in autosomal dominant AD. Nature Neuroscience. 2022. ↩︎ ↩︎
DIAN-Observational Study design. JAMA Neurology. 2023. ↩︎
Benzinger TL, et al. Regional variability of imaging biomarkers. 2013. ↩︎ ↩︎ ↩︎ ↩︎
Fagan AM, et al. Cerebrospinal fluid biomarkers in DIAN. 2014. ↩︎ ↩︎ ↩︎ ↩︎
Bateman RJ, et al. Clinical and biomarker changes. 2012. ↩︎ ↩︎ ↩︎ ↩︎
McDade E, et al. The longitudinal trajectory. 2022. ↩︎ ↩︎
Mills SM, et al. Antiamyloid therapy. 2023. ↩︎ ↩︎
Reiman EM, et al. DIAN and the path. 2019. ↩︎ ↩︎
Goate A, et al. APP mutations. 1991. ↩︎ ↩︎
Sherrington R, et al. Cloning of a novel gene. 1995. ↩︎ ↩︎
Levy-Lahad E, et al. PSEN2 in early-onset. 1995. ↩︎ ↩︎
Villemagne VL, et al. Amyloid imaging in DIAN. 2013. ↩︎ ↩︎
Gordon BA, et al. Tau PET in autosomal dominant. 2018. ↩︎ ↩︎
Lim YY, et al. Cognitive decline. 2017. ↩︎ ↩︎
Jack CR Jr, et al. Hypothetical model of dynamic biomarkers of AD cascade. 2010. ↩︎ ↩︎
Apostolova LG, et al. Neurodegeneration in DIAN. 2022. ↩︎ ↩︎
Patterson BW, et al. Age and cognitive performance in DIAN. 2018. ↩︎ ↩︎
Ryman DC, et al. Symptom onset in autosomal dominant AD. 2015. ↩︎ ↩︎
Salloway S, et al. Anti-amyloid therapy in DIAN-TU. 2024. ↩︎ ↩︎
Millar T, et al. Prevention trials in autosomal dominant AD. 2022. ↩︎ ↩︎
Pankiewicz JE, et al. Amyloid removal in preclinical AD. 2022. ↩︎ ↩︎
Aschenbrenner AJ, et al. Biomarker endpoints in DIAN-TU. 2023. ↩︎ ↩︎
McDade E, et al. Timing of treatment in preclinical AD. 2024. ↩︎ ↩︎
DIAN Data Sharing. Alzheimer's Disease Data Initiative. 2024. 2024. ↩︎ ↩︎
Selkoe DJ, Hardy J. The amyloid hypothesis at 25 years. 2016. ↩︎ ↩︎
Blennow K, et al. Biomarkers for preclinical AD. 2023. ↩︎ ↩︎
Cummings J, et al. Alzheimer's Disease prevention trials. 2024. ↩︎ ↩︎
Aisen PS, et al. The DIAN impact on AD prevention. 2024. ↩︎ ↩︎