Nuclear and cellular, micro and nano calcification in Alzheimer's disease patients and correlation to phosphorylated Tau

Abstract

Brain calcification (calcium phosphate mineral formation) has been reported in the past 100 years in the brains of Alzheimer's disease (AD) patients. However, the association between calcification and AD, the triggers for calcification, and its role within the disease are not clear. On the other hand, hyperphosphorylated Tau protein (pTau) tangles have been widely studied and recognized as an essential factor in developing AD. In this work, calcification in the brains of AD patients is characterized by advanced electron microscopy and fluorescence microscopy. Results are then compared to samples from cognitively healthy, age-matched donors, and the colocalization of calcification and pTau is investigated. Here, we show that AD patients’ brains present microcalcification associated with the neural cell nuclei and cell projections, and that these are strongly related to the presence of pTau. The link between microcalcification and pTau suggests a potential mechanism of brain cell damage. Together with the formation of amyloid plaques and neurofibrillary tangles, microcalcification in neuronal cells adds to a better understanding of the pathology of AD. Finally, the presence of microcalcification in the neuronal cells of AD patients may assist in AD diagnosis, and may open avenues for developing intervention strategies based on inhibition of calcification. Statement of significanceBrain calcification has been reported in the past 100 years in the brains of Alzheimer's disease (AD) patients. However, the association between calcification and AD is not clear. Hyperphosphorylated Tau protein (pTau) has been studied and recognized as a key factor in developing AD. We show here that AD patients’ brains present microcalcification associated with the neuronal cell nuclei and cell projections, and that these are related to the presence of pTau. The study of calcification in brain cells can contribute to a better understanding of the biochemical mechanisms associated with AD and might also reveal that calcification is part of the full disease mechanism. Moreover, this work opens the possibility for using calcification as a biomarker to identify AD.