Cicognola C, et al. - In this investigation, researchers identified new tau (an axonal microtubule-binding protein) fragments and described a possible model for their distribution, function, and role in the pathogenesis of Alzheimer’s disease (AD). Using high-resolution mass spectrometry, they immunoprecipitated tau from cerebrospinal fluid (CSF) and identified several endogenous peptides ending at amino acid (aa) 123 or 224. According to findings, N-123 tau is produced in both central nervous system (CNS) and PNS and represents a general marker of tau metabolism, while N-224 tau is neuron-specific, present in tangles, secreted in CSF and upregulated in AD, indicating a connection between tau cleavage and propagation, pathology of tangles and cognitive decline.