Neuronal cytoskeleton in the biology of Alzheimer disease

In Alzheimer disease the neuronal cytoskeleton is severely affected with the accumulation of paired helical filaments (PHF) in selected neurons, and a defect of microtubule assembly. Although the biochemistry of PHF is not yet completely established, the microtubule associated protein tau has been identified as one of their components. Tau in PHF is abnormally phosphorylated. This alteration of tau is present at very early stages of tangles formation. These findings indicate a defect of the neuronal phosphorylation/dephosphorylation system in Alzheimer brain. It is hypothesized that abnormal phosphorylation, together with other modifications might stabilize tau and facilitate its polymerization together with some other as yet to be identified components to PHF. The microtubule assembly defect might have direct functional consequences via compromised axoplasmic flow and neurotransmission.