Pineal stones have an important function in Alzheimer’s disease

The pineal gland, an endocrine organ located at the brain's geometric center, primarily secretes melatonin to regulate circadian rhythms. Pineal gland calcification (PGC) is the formation of pineal stones, composed of mainly hydroxyapatite. In vivo study using computed tomography showed patients with Alzheimer’s disease (AD) have significantly higher the degree of PGC than controls. However, the biological function of PGC and its alterations in AD remain unknown. Here we show that PGC is part of a brain filtration system that adsorbs metal ions and has a neuroprotective function. This function is diminished due to decreased carbonate substitution in pineal stones of individuals with AD. We identified four main types of pineal stone by surface micromorpho-elemental analysis, indicating a greater surface morphological diversity in AD. Furthermore, AD pineal stone nanocrystals exhibit neuronotoxicity and promote the formation of soluble amyloid-beta (Aβ)42 oligomers. We propose pineal gland radiomics and serum metallomics as tools for auxiliary diagnosis of AD. We anticipate our assay as an initial step towards advancing basic biological research on PGC and understanding its clinical significance in AD.