Predicting biological age using an accumulated neurotoxicity biomarker for amyloid beta oligomers.

This study proposes using accumulated neurotoxicity, defined as the time integral of Aβ 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 Aβ 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 Aβ monomers and oligomers with age accelerates biological aging. Reducing Aβ 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 Aβ 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.