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Updated: Jun 16, 2026
Visualization of Amyloid β Deposits in the Human Brain with Matrix-assisted Laser Desorption/Ionization Imaging Mass Spectrometry
Published on: March 7, 2019
Spatial-Temporal Patterns of β-Amyloid Accumulation: A Subtype and Stage Inference Model Analysis.
Lyduine E Collij1, Gemma Salvadó1, Viktor Wottschel1
1From the Department of Radiology and Nuclear Medicine (L.E.C., V.W., S.E.M., P.S., F.H., A.M.W., B.N.M.B., F.B., I.L.A.), Alzheimer Center and Department of Neurology (W.M.v.d.F., P.S., P.J.V.), and Department of Epidemiology & Data Science (W.M.v.d.F.), Amsterdam UMC, Vrije Universiteit Amsterdam, the Netherlands; Barcelonaβeta Brain Research Center (BBRC) (G.S., J.D.G.), Pasqual Maragall Foundation; IMIM (Hospital del Mar Medical Research Institute) (G.S., J.D.G.), Barcelona, Spain; Stevens Neuroimaging and Informatics Institute (L.A.), Keck School of Medicine, University of Southern California, Los Angeles; Centre for Medical Image Computing and Queen Square Institute of Neurology (F.B.), UCL, UK; Faculty of Medicine of the University of Geneva (S.H.); CIMC-Centre d'Imagerie Médicale de Cornavin (S.H.), Genève, Switzerland; Department of Surgical Sciences, Radiology (S.H.), Uppsala University, Sweden; Department of Radiology (S.H.), Beijing Tiantan Hospital, Capital Medical University, Beijing, China; and Centro de Investigación Biomédica en Red de Bioingeniería, Biomateriales y Nanomedicina (CIBER-BBN) (J.D.G.), Madrid, Spain.
This study reveals three distinct subtypes of beta-amyloid accumulation, challenging the single-trajectory model. These subtypes show unique associations with Alzheimer's disease risk factors, suggesting personalized staging is possible.
Area of Science:
- Neuroimaging
- Biomarkers
- Alzheimer's Disease Research
Background:
- Current beta-amyloid (Aβ) staging models assume a uniform spatial-temporal progression of amyloid accumulation.
- Investigating potential subtypes of Aβ accumulation is crucial for refining staging models and understanding disease heterogeneity.
Purpose of the Study:
- To apply the data-driven Subtype and Stage Inference (SuStaIn) model to amyloid-PET data to identify distinct subtypes of Aβ accumulation.
- To assess the associations between identified subtypes and demographic factors, Alzheimer's disease risk factors, and clinical progression.
Main Methods:
- Pooled amyloid-PET data from 3,010 participants across six cohorts (ALFA+, EMIF-AD, ABIDE, OASIS, ADNI).
- Calculated standardized uptake value ratios for 17 brain regions.
- Applied the SuStaIn algorithm to identify optimal subtypes and stages, with multinomial logistic regression used to assess demographic and risk factor effects.
Main Results:
- A single-subtype model replicated the traditional amyloid trajectory, but SuStaIn identified three optimal subtypes: frontal, parietal, and occipital, based on initial affected regions.
- Significant differences were observed across subtypes in APOE ε4 carrier status, dementia prevalence, and age at onset.
- The frontal subtype showed higher amyloid and CSF p-tau burden, while parietal and occipital subtypes did not differ in this regard. Most participants maintained their subtype assignment at follow-up.
Conclusions:
- The Subtype and Stage Inference (SuStaIn) model identified three distinct subtypes of beta-amyloid accumulation, offering a more nuanced view than the traditional single-trajectory model.
- These subtypes exhibit differential associations with Alzheimer's disease risk factors, highlighting the potential for subtype-specific staging and therapeutic strategies.
- Further research is warranted to determine the clinical utility of these identified subtypes in Alzheimer's disease.
