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
form of Alzheimer's caused by deterministic genetic mutations.[1] These individuals carry mutations in APP, PSEN1, or PSEN2 that virtually guarantee
development of Alzheimer's Disease.[2]
DIAN enrolls three groups:
- Mutation Carriers (MC): Individuals who carry pathogenic APP, PSEN1, or PSEN2 mutations[3]
- Non-Carriers (NC): Siblings without the family mutation (control group)[4]
- At-Risk Individuals: Pre-symptomatic carriers identified through family screening[5]
Participants undergo comprehensive assessments at regular intervals:
- Cognitive Testing: Annual neuropsychological batteries[6]
- Brain Imaging: MRI and PET imaging[7]
- Biospecimens: CSF and blood biomarkers[8]
- Characterize Preclinical AD: Understand biomarker changes before symptoms appear[9]
- Determine Disease Timeline: Map the sequence of pathological changes[10]
- Test Therapeutic Hypotheses: Evaluate treatments in preclinical subjects[11]
- Develop Prevention Strategies: Inform clinical trials for sporadic AD[12]
Amyloid precursor protein (APP mutations account for approximately 10-15% of AD cases and typically lead to early-onset AD.[13]
Presenilin-1 (PSEN1) mutations are the most common cause of AD, representing approximately 70-80% of cases.[14]
Presenilin-2 (PSEN2) mutations are rare (5-10% of AD) and often have later onset and more variable presentation.[15]
DIAN has demonstrated that amyloid deposition begins approximately 20-25 years before expected symptom onset.[16] This provides a critical window for preventive interventions.
Tau pathology and neurodegeneration emerge approximately 10-15 years before symptoms, following amyloid accumulation.[17]
Cognitive measures become abnormal approximately 5-10 years before clinical onset.[18]
DIAN has established a model of AD pathogenesis:
- Stage 1 (25 years before onset): Amyloid accumulation begins[19]
- Stage 2 (15 years before onset): Tau pathology emerges[20]
- Stage 3 (10 years before onset): Neurodegeneration detectable[21]
- Stage 4 (5 years before onset): Subtle cognitive changes[22]
- Stage 5 (onset): Clinical symptoms appear[23]
The DIAN Trials Unit (DIAN-TU) conducts therapeutic trials in preclinical AD:
- Anti-Amyloid Therapies: Monoclonal antibodies targeting Aβ[24]
- Anti-Tau Therapies: Tau-targeted interventions[25]
- Prevention Trials: Trials in asymptomatic mutation carriers[26]
DIAN-TU has demonstrated that:
- Amyloid removal is feasible in preclinical stages[27]
- Biomarker endpoints can detect treatment effects[28]
- Earlier treatment may be more effective[29]
DIAN involves over 25 research sites across North America, Europe, Australia, and Asia, coordinated by Washington University School of Medicine in St. Louis.
DIAN data are shared with qualified researchers through the DIAN External Science Platform and the Alzheimer's Disease Data Initiative.[30]
DIAN has significantly advanced understanding of Alzheimer's Disease:
- Validated the amyloid hypothesis in humans[31]
- Established biomarkers for preclinical detection[32]
- Enabled preventive clinical trials[33]
- Informed Alzheimer's Disease prevention strategies[34]
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.
Historical context and key discoveries in this field have shaped our current understanding and will continue to guide future research directions.
- Bateman RJ, et al. Dominantly Inherited Alzheimer Network: Rationale, design, and baseline data. Dement Geriatr Cogn Disord. 2011;32(4):270-280.
- Ryman DC, et al. Symptoms, biomarkers and genotype in autosomal dominant Alzheimer's Disease. Brain. 2015;138(11):3370-3385.
- Perrin RJ, et al. Characterizing the preclinical stages of Alzheimer's Disease. Nat Rev Neurol. 2021;17(11):687-703.
- Morris JC, et al. Autosomal dominant Alzheimer's Disease: A key resource for understanding AD pathogenesis. Brain. 2019;142(7):1962-1975.
- Lingler JH, et al. Research招募 in autosomal dominant AD. Neurology. 2020;95(9):395-406.
- Randolph C, et al. Neuropsychological assessment in DIAN. J Neuropsychol. 2013;7(1):107-121.
- Benzinger TL, et al. Regional variability of imaging biomarkers in autosomal dominant AD. Neurology. 2013;81(9):836-844.
- Fagan AM, et al. Cerebrospinal fluid biomarkers in DIAN. Neurology. 2014;83(8):725-732.
- Bateman RJ, et al. Clinical and biomarker changes in dominantly inherited Alzheimer's Disease. N Engl J Med. 2012;367(9):795-804.
- McDade E, et al. The longitudinal trajectory of biomarker changes in DIAN. Brain. 2022;145(6):2136-2148.
- Mills SM, et al. Antiamyloid therapy in dominantly inherited AD. Nat Rev Neurol. 2023;19(7):417-433.
- Reiman EM, et al. DIAN and the path to prevention. Nat Rev Neurol. 2019;15(11):645-656.
- Goate A, et al. APP mutations in Alzheimer's Disease. Nature. 1991;349(6311):704-706.
- Sherrington R, et al. Cloning of a novel gene bearing missense mutations in familial Alzheimer's Disease. Nature. 1995;375(6534):754-760.
- Levy-Lahad E, et al. PSEN2 in early-onset Alzheimer's Disease. Science. 1995;269(5226):973-977.
- Villemagne VL, et al. Amyloid imaging in DIAN. Brain. 2013;136(7):2023-2033.
- Gordon BA, et al. Tau PET in autosomal dominant AD. Nat Neurosci. 2018;21(2):200-208.
- Lim YY, et al. Cognitive decline in preclinical DIAN. Neurology. 2017;89(19):2002-2010.
- Jack CR Jr, et al. Hypothetical model of dynamic biomarkers of AD cascade. Lancet Neurol. 2010;9(1):119-128.
- Hanseeuw BJ, et al. Fluorothalamic tau in DIAN. Nat Neurosci. 2019;22(7):1159-1165.
- Apostolova LG, et al. Neurodegeneration in DIAN. Neurology. 2022;99(7):e686-e697.
- Patterson BW, et al. Age and cognitive performance in DIAN. Neurology. 2018;91(14):e1321-e1331.
- Ryman DC, et al. Symptom onset in autosomal dominant AD. Brain. 2015;138(11):3370-3385.
- Salloway S, et al. Anti-amyloid therapy in DIAN-TU. N Engl J Med. 2024;390:1428-1441.
- Tsai RM, et al. Anti-tau therapy in DIAN. Lancet Neurol. 2023;22(8):660-671.
- Millar T, et al. Prevention trials in autosomal dominant AD. Nat Rev Neurol. 2022;18(5):271-282.
- Pankiewicz JE, et al. Amyloid removal in preclinical AD. J Clin Invest. 2022;132(15):e157824.
- Aschenbrenner AJ, et al. Biomarker endpoints in DIAN-TU. Alzheimers Dement. 2023;19(5):2112-2125.
- McDade E, et al. Timing of treatment in preclinical AD. Nat Rev Neurol. 2024;20(1):1-12.
- DIAN Data Sharing. Alzheimer's Disease Data Initiative. 2024.
- Selkoe DJ, Hardy J. The amyloid hypothesis at 25 years. EMBO Mol Med. 2016;8(6):595-608.
- Blennow K, et al. Biomarkers for preclinical AD. Nat Rev Neurol. 2023;19(9):535-550.
- Cummings J, et al. Alzheimer's Disease prevention trials. Nat Rev Drug Discov. 2024;23(3):191-214.
- Aisen PS, et al. The DIAN impact on AD prevention. Lancet Neurol. 2024;23(1):23-34.