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Alzheimer's Association International Conference 2026

July 12-15, 2026 | London, United Kingdom, and Online

2682

Multimodal Markers Of Early Alzheimer's Disease-related Change In Adults With Down Syndrome

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Poster Presenter

Mina Idris

Authors

Mina Idris, Fedal Saini, Phoebe Ivain, Leda Bianchi, Henrik Zetterberg, Peter Wijeratne, Andre Strydom

Affiliations

King's College London, UK, University of Gothenburg, Sweden, University of Sussex, UK

Part of Topic

Multimodal Modelling of Early Alzheimer's Disease-Related Change in Adults with Down Syndrome

Mina Idris1, Fedal Saini1, Phoebe Ivain1, Leda Bianchi1, Henrik Zetterberg2, Peter Wijeratne3 & André Strydom1 | mina.idris@kcl.ac.uk

1King's College London, UK, 2University of Gothenburg, Sweden, & 3University of Sussex, UK.

Multimodal modelling suggests structural MRI and plasma biomarker abnormalities emerge before cognitive and functional decline in adults with Down syndrome.

INTRODUCTION

•Adults with Down syndrome (DS) are at high risk of Alzheimer's disease (AD) due to triplication of the amyloid precursor protein gene.1

•Although AD neuropathology is common by mid-adulthood, the relative timing of biological, cognitive, and functional changes is unclear.

•Aim: To integrate structural MRI, plasma, cognition measures within a single AD progression model.

METHODS

Multimodal marker assessment

•MRI: Hippocampus, Thalamus, Caudate, Precuneus, Posterior cingulate cortex, Mean cortical thickness, Lateral ventricles

•Plasma : GFAP, NfL, pTau217

•Cognition: CANTAB PAL

•Informant report: DLD

Analysis

•Markers showing age-related disease signal were entered into an Event-Based Model (EBM), which estimates the most likely sequence of marker abnormality.2

RESULTS

Table 1. London Down Syndrome consortium (LonDownS) MRI cohort

Figure 1. EBM positional variance diagram of AD-related markers

Increased GFAP → Deep grey matter atrophy → Increased pTau217 & NfL → Cortical thinning → Memory decline → Functional decline → Ventricular enlargement

Figure 2. Stage increases with age but varies between individuals

KEY OBSERVATIONS

•Plasma biomarkers showed early age-related abnormalities.

•MRI abnormalities were detected in AD-vulnerable regions.

•Memory-related measures became abnormal before functional decline.

•Informant-reported decline occurred later in the AD cascade.

CONCLUSIONS

•Early changes: Structural MRI and plasma abnormalities emerged first; followed by cognitive and functional decline later.

•Disease sequence: Multimodal EBM identified a biologically plausible sequence of AD-related change in DS.

•Clinical utility: Multimodal disease staging may support early detection and clinical trial enrichment.

CLINICAL IMPLICATIONS

•Early detection: Blood biomarkers and MRI may identify disease-related change decades before AD diagnosis.

•Participant stratification: Disease staging may help identify individuals at elevated risk for prevention trials.

•Precision medicine: Multimodal staging captures heterogeneity between individuals of the same age.

REFERENCES

1. Wiseman FK, et al. Nat Rev Neurosci. 2015;16:564-574.

2. Fonteijn HM, et al. Neuroimage. 2012;60(3):1880-1889.

King's College London, The LonDownS Consortium, The Baily Thomas Charitible Fund.

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