Unexpected abundance of pathological tau in progressive supranuclear palsy white matter.
OBJECTIVE
To investigate whether biochemical insoluble tau with 4 (4R) and/or 3 (3R) microtubule-binding repeats accumulate in white as well as gray matter in progressive supranuclear palsy (PSP), a neurodegenerative tauopathy.


METHODS
To assess tau pathology in PSP white matter, we combined Western blot (WB) and immunohistochemical methods to analyze 23 autopsy-confirmed PSP brains.


RESULTS
WBs showed an unexpected abundance of insoluble tau in white and gray matter of PSP brains, but biochemical tau pathology in white matter was not correlated with immunohistochemistry using the same panel of epitope-specific anti-tau antibodies used for WB. Despite heterogeneity in the representation of pathological 3R and 4R tau isoforms in cortical versus subcortical regions, biochemically detectable white matter tau pathology is a constant feature of PSP.


CONCLUSIONS
These studies show additional similarities between PSP and corticobasal degeneration, but unlike corticobasal degeneration, more abundant white matter tau pathology in PSP is detectable by WB than by immunohistochemistry. The differential detection of abnormal tau by biochemistry versus microscopy in PSP may reflect distinct pathological mechanisms, and elucidation of these processes will augment efforts to develop better strategies for the diagnosis and treatment of PSP and related neurodegenerative tauopathies.
Zhukareva
Victoria
V
Department of Pathology and Laboratory Medicine, Center for Neurodegenerative Disease Research, University of Pennsylvania School of Medicine, Philadelphia, PA 19104-4283, USA.
Joyce
Sonali
S
Schuck
Teresa
T
Van Deerlin
Vivianna
V
Hurtig
Howard
H
Albin
Roger
R
Gilman
Sid
S
Chin
Steven
S
Miller
Bruce
B
Trojanowski
John Q
JQ
Lee
Virginia M-Y
VM
D000368:Aged; D000369:Aged, 80 and over; D001053:Apolipoproteins / Q000235:genetics; D015153:Blotting, Western / Q000379:methods; D001921:Brain / Q000187:drug effects / Q000378:metabolism* / Q000473:pathology*; D004268:DNA-Binding Proteins / Q000378:metabolism; D003902:Detergents / Q000494:pharmacology; D005260:Female; D006801:Humans; D007150:Immunohistochemistry / Q000379:methods; D008297:Male; D008875:Middle Aged; D063146:Polycomb-Group Proteins; D011180:Postmortem Changes; D013494:Supranuclear Palsy, Progressive / Q000235:genetics / Q000378:metabolism / Q000473:pathology*; D024801:Tauopathies / Q000235:genetics / Q000378:metabolism / Q000473:pathology*; D014157:Transcription Factors / Q000378:metabolism; D016875:tau Proteins / Q000378:metabolism*
D001053:Apolipoproteins; D004268:DNA-Binding Proteins; D003902:Detergents; C054369:MAPT protein, human; C112309:PHF1 protein, human; D063146:Polycomb-Group Proteins; D014157:Transcription Factors; D016875:tau Proteins