PHF-Core Tau as the Potential Initiating Event for Tau Pathology in Alzheimer’s Disease

Nabil Itzi Luna-Viramontes, B. Berenice Campa-Córdoba, Miguel Angel Ontiveros-Torres, Charles R Harrington, Ignacio Villanueva-Fierro, Parménides Guadarrama-Ortíz, Linda Garcés-Ramírez, Fidel de la Cruz, Mario Hernandes-Alejandro, Sandra Martínez-Robles, Erik González-Ballesteros, Mar Pacheco-Herrero* (Corresponding Author), José Luna-Muñoz* (Corresponding Author)

*Corresponding author for this work

Research output: Contribution to journalArticle

Abstract

Worldwide, around 50 million people have dementia. Alzheimer’s disease (AD) is the most common type of dementia and one of the major causes of disability and dependency among the elderly worldwide. Clinically, AD is characterized by impaired memory accompanied by other deficiencies in the cognitive domain. Neuritic plaques (NPs) and neurofibrillary tangles (NFTs) are histopathological lesions that define brains with AD. NFTs consist of abundant intracellular paired helical filaments (PHFs) whose main constituent is tau protein. Tau undergoes posttranslational changes including hyperphosphorylation and truncation, both of which favor conformational changes in the protein. The sequential pathological processing of tau is illustrated with the following specific markers: pT231, TG3, AT8, AT100, and Alz50. Two proteolysis sites for tau have been described—truncation at glutamate 391 and at aspartate 421—and which can be demonstrated by reactivity with the antibodies 423 and TauC-3, respectively. In this review, we describe the molecular changes in tau protein as pre-NFTs progress to extracellular NFTs and during which the formation of a minimal nucleus of the filament, as the PHF core, occurs. We also analyzed the PHF core as the initiator of PHFs and tau phosphorylation as a protective neuronal mechanism against the assembly of the PHF core.
Original languageEnglish
Article number247
Number of pages11
JournalFrontiers in cellular neuroscience
Volume14
DOIs
Publication statusPublished - 10 Sep 2020

Keywords

  • tau protein
  • tau pathology
  • PHF core
  • Truncation
  • phosphorylation
  • conformational changes
  • paired helical filament
  • neurofibrillary tangles

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