Propagation of tau and Braak’s extension paradigm

Propagation of tau and Braak's extension paradigm

Shigeo Murayama¹⁾, Yuko Saito²⁾

¹⁾Department of Neurology and Neuropathology (the Brain Bank for Aging Research)
²⁾Department of Pathology and Laboratory Medicine

Tau is a microtubule associated protein and biochemically forms the core of neurofibrillary tangles (NFT) in Alzheimer disease (AD). Tau consists of six isoforms with alternative splicing from a single tau gene located on chromosome 17, which are classified into three-repeat (R) and four-R tau, reflecting the number of microtubule binding sites. NFT in AD is unique in being composed of 3+4 R tau and ultrastructurally consists of paired helical filaments (PHF). Braak analyzed elderly brains with Gallyas silver staining and demonstrated that the propagation of ADNFT was in reverse with human cortical developmental stage:starting from entorhinal area (Stage I and II), spreading to limbic system (III and IV), reaching association neocortex (V) and finally involving the primary motor area (VI). Braak's staging is applicable to human aging process and late onset AD. The Braak's staging method is modified by European Confederation of Neuropathological Societies employing the anti-phosphorylated tau (AT8) immunostaining, or by NIA (National Institute of Aging)-AA (Alzheimer Association) 2014 Guidelines with Bielschowsky staining. The propagation or prionoid hypothesis of tau based on the Braak's staging is one of the major topic in the field of AD research at present.

Address correspondence to Dr. Shigeo Murayama, Department of Neurology and Neuropathology (the Brain Bank for Aging Research) (35-2 Sakae-chou, Itabashi- ku, Tokyo 173-0015, Japan)