Individual and regional variations of phospho-tau species in progressive supranuclear palsy

TY - JOUR

T1 - Individual and regional variations of phospho-tau species in progressive supranuclear palsy

AU - Puig, Berta

AU - Rey, María Jesus

AU - Ferrer, Isidre

AU - Puig Martorell, Berta

PY - 2005/9/1

Y1 - 2005/9/1

N2 - The purpose of this study was to learn about possible variations in phospho-tau profiles in terms of case-to-case differences, regional modifications and diversification of tau phosphorylation sites in five PSP cases with moderate to severe frontosubcortical dysfunction. Gel electrophoresis of sarkosyl-insoluble fractions and Western blotting with five anti-tau phospho-specific antibodies directed to phosphorylation sites Thr181, Ser202, Ser214, Ser396 and Ser422 were used to study four brain regions including frontal cortex, area 8, subcortical white matter of the frontal lobe, caudate/putamen: striatum, and basis pontis: pons. Although two bands of 66 and 62 kDa were observed in almost every region in each case, the intensity of the bands depends on the anti-tau phospho-specific antibody. More importantly, bands of 72, 50/55 and 37 kDa were commonly found in PSP brains, whereas other bands of about 60, 42, 33 and 29 kDa were irregularly observed. The pattern of bands differed slightly from one case to another and from one region to another. Moreover, the phospho-tau profile differed depending on the anti-tau phospho-specific antibody used. These data suggest that several species of tau are variably phosphorylated at a given time in a given region (and probably in a given cell), and that tau aggregates are composed of several phosphorylated truncated or cleaved tau molecules, in addition to phosphorylated complete tau isoforms.

AB - The purpose of this study was to learn about possible variations in phospho-tau profiles in terms of case-to-case differences, regional modifications and diversification of tau phosphorylation sites in five PSP cases with moderate to severe frontosubcortical dysfunction. Gel electrophoresis of sarkosyl-insoluble fractions and Western blotting with five anti-tau phospho-specific antibodies directed to phosphorylation sites Thr181, Ser202, Ser214, Ser396 and Ser422 were used to study four brain regions including frontal cortex, area 8, subcortical white matter of the frontal lobe, caudate/putamen: striatum, and basis pontis: pons. Although two bands of 66 and 62 kDa were observed in almost every region in each case, the intensity of the bands depends on the anti-tau phospho-specific antibody. More importantly, bands of 72, 50/55 and 37 kDa were commonly found in PSP brains, whereas other bands of about 60, 42, 33 and 29 kDa were irregularly observed. The pattern of bands differed slightly from one case to another and from one region to another. Moreover, the phospho-tau profile differed depending on the anti-tau phospho-specific antibody used. These data suggest that several species of tau are variably phosphorylated at a given time in a given region (and probably in a given cell), and that tau aggregates are composed of several phosphorylated truncated or cleaved tau molecules, in addition to phosphorylated complete tau isoforms.

KW - Aged

KW - Amino Acid Sequence

KW - Binding Sites

KW - Blotting, Western

KW - Brain

KW - Electrophoresis, Gel, Two-Dimensional

KW - Female

KW - Humans

KW - Male

KW - Molecular Weight

KW - Neurons

KW - Peptide Fragments

KW - Phosphorylation

KW - Serine

KW - Supranuclear Palsy, Progressive

KW - Threonine

KW - tau Proteins

U2 - 10.1007/s00401-005-1046-0

DO - 10.1007/s00401-005-1046-0

M3 - SCORING: Journal article

C2 - 15973541

VL - 110

SP - 261

EP - 268

JO - ACTA NEUROPATHOL

JF - ACTA NEUROPATHOL

SN - 0001-6322

IS - 3

ER -