OECD Series on Adverse Outcome Pathways
An Adverse Outcome Pathway (AOP) describes a logical sequence of causally linked events at different levels of biological organisation, which follows exposure to a stressor and leads to an adverse health effect in humans or wildlife. AOPs are the central element of a toxicological knowledge framework, promoted by member countries through OECD, built to support chemical risk assessment based on mechanistic reasoning. These AOPs are available in the AOP-Wiki, an interactive and virtual encyclopaedia for AOP development. Following their development and review, the endorsed AOPs are published in the OECD Series on Adverse Outcome Pathways. As scientific knowledge progresses, the publication of an AOP in this series does not preclude regular updates or new contributions to a given AOP. While the AOP-Wiki is a dynamic tool, only impactful changes to the AOP will be reflected in subsequent updates of the published AOP.
- ISSN : 2415170X (en ligne)
- https://doi.org/10.1787/2415170X
Adverse Outcome Pathway on chronic binding of antagonist to N-methyl-D-aspartate receptors during brain development leading to neurodegeneration with impairment in learning and memory in aging
This AOP links chronic NMDA receptors inhibition during brain development to
neurodegeneration in hippocampus and cortex with amyloid plaque deposition and tau
hyperphosphorylation, and impairment of learning and memory, which are considered as
hallmark of Alzheimer's disease. It makes use of some KEs and KERs from AOP 13 and
introduces Neuroinflammation as KE, which is involved in several neurodegenerative
diseases. This AOP is based on the hypothesis of Landrigan and coworkers (2005)
proposing an early origin of neurodegenerative diseases in later life. The chemical initiator
used in this AOP for the empirical support is lead (Pb). In adults, cumulative lifetime Pb
exposure is also associated with decline in cognition, suggesting that long-term exposure
during development or occupational exposure increases the risk to develop
neurodegenerative disease. The long latency period between exposure and late-onset of
effects gives a very broad life-stage applicability. The gap of knowledge is mainly due to
limited quantitative evaluations.