Selective tau tyrosine nitration in non-AD tauopathies

Area of Science:

• Neuroscience
• Biochemistry
• Pathology

Background:

• Alzheimer's disease (AD) is characterized by tau pathology.
• Novel antibodies targeting nitrated tau (Tau-nY197, Tau-nY394) were previously identified.
• The occurrence of tau nitration in other tauopathies remained unclear.

Purpose of the Study:

• To investigate tau nitration at tyrosine 197 and 394 in corticobasal degeneration (CBD), progressive supranuclear palsy (PSP), and Pick's disease (PiD).
• To compare the reactivity of Tau-nY197 and Tau-nY394 with previously characterized antibodies Tau-nY18 and Tau-nY29.
• To determine if tau nitration is a disease-specific and controlled modification in tauopathies.

Main Methods:

• Western blotting and immunohistochemistry (IHC) were employed.
• The study utilized antibodies specific for tau nitrated at tyrosine 18, 29, 197, and 394.
• Pathological lesions in CBD, PSP, and PiD brain tissues were analyzed.

Main Results:

• Tau-nY18 showed limited labeling in PiD.
• Tau-nY29 labeled some tau inclusions in CBD and PSP, and Pick body inclusions in PiD.
• Tau-nY197 labeled neuropil threads in CBD and PSP, and Pick bodies in PiD; Tau-nY394 showed no reactivity.
• Extensive tau pathology was labeled by Tau-Y197, which recognizes the Y-197-containing proline-rich region.

Conclusions:

• Tau nitration at tyrosine 29 may be a pathological modification associated with neurodegeneration.
• Site-specific tau tyrosine nitration occurs in a disease and lesion-specific manner.
• Nitration appears to be a highly controlled modification in both AD and non-AD tauopathies.