Interpretable AI Powered Prognosis Tool for β-Amyloid Plaque Burden

We developed interpretable machine learning models to predict five-year β-Amyloid (Aβ) plaque progression in individuals at early risk for Alzheimer’s Disease (AD). Focusing on subjects with initially low Aβ burden (Centiloid < 24) from the ADNI cohort, we integrated demographic information, APOE genotype, cognitive assessments, and PET-derived features—including regional SUVRs, brain volumes and their change rates. Using support vector machine, random forest, and multilayer perceptron models, we achieved strong performance (F1-scores up to 0.866), with consistent generalization to the independent OASIS-3 dataset.

To ensure transparency, we applied SHAP (Shapley Additive Explanations) and found that changes in prefrontal SUVR, regional volumes, and SUVRs in parietal and posterior cingulate regions were among the most influential predictors. Our approach offers an interpretable and practical tool for identifying individuals at high risk of Aβ buildup, supporting early diagnosis and timely intervention in AD.

A: Prognosis pipeline for β-Amyloid plaque burden.
B: ML model performance (weighted F1-score).
C: PET feature contributions based on averaged normalized SHAP values from MLP outputs.

Longitudinal analysis on epileptogenesis in Alzheimer’s Disease

Alzheimer’s disease (AD), which accounts for ~70% of dementia cases, shares key mechanisms with late-onset epilepsy, including neuroinflammation and amyloid buildup. Seizures further accelerate Aβ and tau accumulation, worsening cognitive decline, as seen in hAPP-J20 mice.

We conducted a longitudinal study tracking spatial learning, memory loss, and Aβ plaque buildup in Tg and non-Tg mice from birth to 27 weeks. Behavioral tests, immunostaining (NPY, CaMK2, PV), and video-EEG were performed every 3 weeks.

Our results link Aβ deposition to seizure activity, reduced neuronal density, and rising HFOs, especially fast ripples and pathological ripples, highlighting their potential as early biomarkers of epileptogenesis in AD.

Temporal analysis of HFO incidence from chronic CA1 recordings: Ripple (80–200 Hz, top) and fast ripple (250–500 Hz, bottom) rates were similar between nTg and Tg mice before 15 weeks (pre-plaque stage), but showed a significant increase in Tg mice after 17–18 weeks.

Published Paper: https://alz-journals.onlinelibrary.wiley.com/doi/10.1002/alz.087939