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bioRxiv · 10.1101/2025.02.28.640920

Predicting Biological Age Using an Accumulated Neurotoxicity Biomarker for Amyloid Beta Oligomers

Kuznetsov, A. V.
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Abstract

This study proposes using accumulated neurotoxicity, defined as the time integral of A{beta} oligomer concentration, as a biomarker for neuronal aging. A relationship between biological age and accumulated neurotoxicity is proposed. Numerical analysis guided the development of a new analytical solution linking the biological and calendar ages of neurons. The effects of A{beta} monomer and oligomer half-lives--key indicators of proteolytic efficiency--on biological age are examined. Both constant and age-dependent (exponentially increasing) half-life scenarios are considered. The findings indicate that increasing the half-life of A{beta} monomers and oligomers with age accelerates biological aging. Reducing A{beta} monomer production is shown to slow biological aging, with a linear relationship established between these two quantities. Additionally, biological age is found to depend linearly on the half-deposition time of A{beta} oligomers into senile plaques. The model demonstrates that biological age is irreversible, providing a theoretical explanation for why plaque-clearing therapies cannot reverse established cognitive impairment. The model also demonstrates that biological age is path-dependent rather than state-dependent.

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Kuznetsov, A. V.. 2025-03-06. Predicting Biological Age Using an Accumulated Neurotoxicity Biomarker for Amyloid Beta Oligomers. https://doi.org/10.1101/2025.02.28.640920

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