Time Factor Hypothesis: Towards Identifying Onset of Alzheimer’s Disease in Younger Adults

Abstract

Introduction: Several hypotheses explain the onset and pathology of Alzheimer’s disease (AD), such as the amyloid hypothesis and the tau hypothesis. Consequently, various biomarkers have been identified and drugs developed, but the fight against the AD epidemic is still ongoing. Perhaps it is time to explore new hypotheses. To begin with, researchers have shown that neuropathology associated with AD typically starts to develop decades before the clinical onset or manifestation of the disease. However, therapeutic interventions are still being designed to address mild-to-moderate stages of the disease, which are unfortunately irreversible. Methods: We have reviewed various mathematical models to identify any missing parameters that could support the proposed time factor hypothesis for AD. In addition, we have developed a cognitive function algorithm that utilizes the identified parameters. The algorithm’s results are used to predict the likelihood of neuritic dystrophy. Results: With mathematical evidence, we emphasize the importance of timely diagnosis of AD and provide support for considering an earlier age of 30 years (rather than 60 years or older) for effective interventions, including diagnosis and drug development. Discussion: Among other points, we showed that Aβ42 aggregation starts around age 30–40 years. With this information, we propose the need to re-engineer the concepts behind the science of AD. The number of AD patients will experience a nose dive if effort aimed at timely prevention of (for instance) Aβ42 aggregation is expended.