TY - JOUR
T1 - Molecular Processing of Tau Protein in Progressive Supranuclear Palsy
T2 - Neuronal and Glial Degeneration
AU - Martínez-Maldonado, Alejandra
AU - Ontiveros-Torres, Miguel Ángel
AU - Harrington, Charles R.
AU - Montiel-Sosa, José Francisco
AU - Prandiz, Raúl Garciá Tapia
AU - Bocanegra-López, Patricia
AU - Sorsby-Vargas, Andrew Michael
AU - Bravo-Muñoz, Marely
AU - Florán-Garduño, Benjamín
AU - Villanueva-Fierro, Ignacio
AU - Perry, George
AU - Garcés-Ramírez, Linda
AU - De La Cruz, Fidel
AU - Martínez-Robles, Sandra
AU - Pacheco-Herrero, Mar
AU - Luna-Muñoz, José
N1 - Publisher Copyright:
© 2021 - The authors. Published by IOS Press.
PY - 2021
Y1 - 2021
N2 - Background: Alzheimer's disease (AD) and progressive supranuclear palsy (PSP) are examples of neurodegenerative diseases, characterized by abnormal tau inclusions, that are called tauopathies. AD is characterized by highly insoluble paired helical filaments (PHFs) composed of tau with abnormal post-translational modifications. PSP is a neurodegenerative disease with pathological and clinical heterogeneity. There are six tau isoforms expressed in the adult human brain, with repeated microtubule-binding domains of three (3R) or four (4R) repeats. In AD, the 4R:3R ratio is 1:1. In PSP, the 4R isoform predominates. The lesions in PSP brains contain phosphorylated tau aggregates in both neurons and glial cells. Objective: Our objective was to evaluate and compare the processing of pathological tau in PSP and AD. Methods: Double and triple immunofluorescent labeling with antibodies to specific post-translational tau modifications (phosphorylation, truncation, and conformational changes) and thiazin red (TR) staining were carried out and analyzed by confocal microscopy. Results: Our results showed that PSP was characterized by phosphorylated tau in neurofibrillary tangles (NFTs) and glial cells. Tau truncated at either Glu391 or Asp421 was not observed. Extracellular NFTs (eNFTs) and glial cells in PSP exhibited a strong affinity for TR in the absence of intact or phosphorylated tau. Conclusion: Phosphorylated tau was as abundant in PSP as in AD. The development of eNFTs from both glial cells and neuronal bodies suggests that truncated tau species, different from those observed in AD, could be present in PSP. Additional studies on truncated tau within PSP lesions could improve our understanding of the pathological processing of tau and help identify a discriminatory biomarker for AD and PSP.
AB - Background: Alzheimer's disease (AD) and progressive supranuclear palsy (PSP) are examples of neurodegenerative diseases, characterized by abnormal tau inclusions, that are called tauopathies. AD is characterized by highly insoluble paired helical filaments (PHFs) composed of tau with abnormal post-translational modifications. PSP is a neurodegenerative disease with pathological and clinical heterogeneity. There are six tau isoforms expressed in the adult human brain, with repeated microtubule-binding domains of three (3R) or four (4R) repeats. In AD, the 4R:3R ratio is 1:1. In PSP, the 4R isoform predominates. The lesions in PSP brains contain phosphorylated tau aggregates in both neurons and glial cells. Objective: Our objective was to evaluate and compare the processing of pathological tau in PSP and AD. Methods: Double and triple immunofluorescent labeling with antibodies to specific post-translational tau modifications (phosphorylation, truncation, and conformational changes) and thiazin red (TR) staining were carried out and analyzed by confocal microscopy. Results: Our results showed that PSP was characterized by phosphorylated tau in neurofibrillary tangles (NFTs) and glial cells. Tau truncated at either Glu391 or Asp421 was not observed. Extracellular NFTs (eNFTs) and glial cells in PSP exhibited a strong affinity for TR in the absence of intact or phosphorylated tau. Conclusion: Phosphorylated tau was as abundant in PSP as in AD. The development of eNFTs from both glial cells and neuronal bodies suggests that truncated tau species, different from those observed in AD, could be present in PSP. Additional studies on truncated tau within PSP lesions could improve our understanding of the pathological processing of tau and help identify a discriminatory biomarker for AD and PSP.
KW - Alzheimer's disease
KW - neurofibrillary tangle
KW - progressive supranuclear palsy
KW - tau protein
KW - truncation
UR - http://www.scopus.com/inward/record.url?scp=85101258768&partnerID=8YFLogxK
U2 - 10.3233/JAD-201139
DO - 10.3233/JAD-201139
M3 - Artículo
C2 - 33459640
AN - SCOPUS:85101258768
SN - 1387-2877
VL - 79
SP - 1517
EP - 1531
JO - Journal of Alzheimer's Disease
JF - Journal of Alzheimer's Disease
IS - 4
ER -