Alzheimer disease—The proposed role of tanycytes in the formation of tau tangles and amyloid beta plaques in human brain

The causes of Alzheimer Disease (AD) are attributed to the formation of abnormal protein deposits including tau tangles and Amyloid ß (Aβ) plaques. These proteins are believed to accumulate in the cortex due to impaired waste removal resulting in neurodegeneration. Interestingly, removal of these protein accumulations has failed to halt disease progression. How can this be explained? We have recently proposed the existence of a tanycyte-derived canal-system in the brain that likely internalizes neuronal waste. We propose that Aβ and tau protein may play important structural roles in this canal system that swells in AD-affected brain. Using in situ hybridization, immunohistochemistry, ultrastructural, and histological methodologies, here we demonstrate the formation of receptacles from translucent ‘swell-bodies’ that form along tanycyte processes. We show that both spatial distribution and anatomical appearance of swell-bodies differ from myelin-forming ependymal tanycytes. Interestingly, receptacles that differentiate within swell-bodies express mRNA for aquaporin4 and the AD-related proteins Presenilin1 and amyloid precursor protein. Consistent with these findings we show strong Aβ immunolabeling of these receptacles that swell and proliferate in AD-affected brain and take on the appearance of Aβ plaques. We conclude that it is likely pathological abnormalities of the associated tanycytes leads to this abnormal swelling.