February 8, 1991Science
A68: a Major Subunit of Paired Helical Filaments and Derivatized Forms of Normal Tau
Authors
Discussion
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Implication
Biochemical analysis demonstrates abnormal phosphorylation transforms normal tau into Alzheimer paired helical filament subunits, indicating aberrant phosphorylation drives neurofibrillary pathology.
Key Points
- To determine the structural and biochemical identity of the Alzheimer disease-specific A68 protein and its relationship to paired helical filaments and normal human tau.
- Purified putative Alzheimer disease-specific A68 proteins to homogeneity from paired helical filaments.
- Compared the amino acid sequence, immunological profile, and apparent relative molecular mass of A68 against normal human tau.
- Performed enzymatic dephosphorylation of A68 and mapped phosphate acceptor sites, specifically targeting the LysSerProVal motif.
- Identified A68 as a major structural subunit of paired helical filaments sharing an identical amino acid backbone with normal human tau.
- Observed that enzymatic dephosphorylation reduces the elevated apparent relative molecular mass of A68 to approximately that of normal tau.
- Showed that the serine residue within the LysSerProVal motif acts as an abnormal phosphate acceptor site in A68 but remains unphosphorylated in normal human tau.
Cite This Study
Lee et al. (1991) studied this question.