AD2, a phosphorylation-dependent monoclonal antibody directed against tau proteins found in Alzheimer's disease.
Alzheimer's disease is characterized by an intraneuronal aggregation of hyperphosphorylated tau proteins into paired helical filaments. The hyperphosphorylation of tau proteins induces a decrease in their electrophoretic mobility, resulting in a pathological tau triplet referred to as tau 55, 64 and 69 or tau-PHF. We have developed monoclonal antibodies directed against this pathological tau triplet. In the present article, we report the properties of antibody AD2, which detects the hyperphosphorylated tau proteins forming paired helical filaments during Alzheimer's disease. Using immunoblotting, AD2 exclusively labeled the tau triplet, while normal tau proteins from control cases were not immunodetected. Furthermore, AD2 is highly specific in that it was able to detect the triplet not only in tau preparations but also in total brain homogenates from Alzheimer's disease patients. The binding of this monoclonal antibody to tau proteins is phosphorylation dependent. Characterization of this antibody allowed us to identify its epitope as containing phosphorylated Ser-396 with the participation of phosphorylated Ser-404. AD2 was also shown to label normal tau proteins from rapidly processed brain tissues, but its epitope is rapidly dephosphorylated during postmortem intervals. However, in autopsic brains, AD2 still represents a valuable tool to investigate neurofibrillary degeneration at the biochemical and immunocytochemical levels.
Buée-Scherrer
V
V
INSERM U422, Lille, France.
Condamines
O
O
Mourton-Gilles
C
C
Jakes
R
R
Goedert
M
M
Pau
B
B
Delacourte
A
A
D000293:Adolescent; D000328:Adult; D000368:Aged; D000544:Alzheimer Disease / Q000276:immunology*; D001921:Brain / Q000276:immunology*; D002648:Child; D002675:Child, Preschool; D005260:Female; D006801:Humans; D015151:Immunoblotting; D008297:Male; D008875:Middle Aged; D010766:Phosphorylation; D016875:tau Proteins / Q000276:immunology*
D016875:tau Proteins