Alzheimer’s disease (AD) is the most common form of dementia worldwide affecting nearly 40 million individuals. While the exact pathophysiology of AD remains to be elucidated it is known that the risk of AD increases with aging. It is appreciated that aging results in changes that can include neuronal atrophy, increased neuroinflammation, and vascular damage. However, it is unknown what factors exacerbate the natural aging process driving disease progression.
Kynurenine metabolites have been shown to be either neuroprotective or neurotoxic, as such the pathway has been investigated in AD. A recent study published by Dr. Marcela Cespedes et al. in Neurobiology of Disease looked at systemic changes in the kynurenine pathway (KP) with the hopes of identifying biomarkers of dementia. This study used samples from nearly 300 individuals who participated in a longitudinal study of aging in Australia. Individuals were grouped into three cohorts; Baseline (AD diagnosis at enrollment), Progressor (AD at a follow-up), and Non-progressors (no AD diagnosis at follow-up). Progressors had increased levels of 3-hydroxyanthranilic acid (3-HAA) and the 3-HAA/anthranilic acid (AA) ratio at baseline. Notably, increased 3-HAA/AA ratio levels at baseline were a strong predictor for progressors (Odds Ratio 35.3). Progressors also had low levels of picolinic acid (PIC) and quinolinic acid (QUIN)/kynurenic acid ratio at baseline as compared to non-progressors. However, this finding was not associated with cognitive decline. This study confirms that the KP metabolites are altered in AD and might predict which individuals will progress. Early detection of AD is critical so that treatment can start prior to irreversible damage occurs. We will be diving further into the KP and aging in our upcoming newsletter (issue 3). Stay tuned!