CDK5 and Neurofibrillary tangles: According to our neuroimmunomodulation theory, alterations in the cross-talks between glial cells and neurons as a consequence of the activity of damage signals, e.g., iron overload, vitamin B deficiencies, Aβ peptide, and also tau oligomers released to extracellular media, [14] trigger the production of proinflammatory cytokines that finally affect neurons by activating the protein kinases CDK5 and GSK3-β, with the consequent tau hyperphosphorylations and aggregation into pathological PHFs and NFTs (Figure 1).