Work

Tau Phosphorylation as an Adaptive Physiological Response: Implications for the Therapy of Tauopathies

Year: 2026

Type: article

Abstract: Recent evidence demonstrates that tau phosphorylation, traditionally viewed as a hallmark of neurodegeneration, also occurs in completely reversible physiological contexts such as mammalian hibernation and human neonatal development. These findings challenge the classical protein-centric "proteinopathy" model of Alzheimer's disease (AD) and other tauopathies. Instead, we propose that phosphorylated tau (p-tau) functions as an adaptive molecular response to metabolic or neuronal activity shifts, and that tauopathies such as AD represent a failure of broader mechanisms that normally restore tau protein homeostasis. Therapeutic strategies should focus on restoring tau protein homeostasis and functionality rather than simply removing phosphorylated species. To achieve this, we discuss one possible therapeutic strategy: dismantling aggregated tau species.

Source: The FASEB Journal

DOI: 10.1096/fj.202503803r

Authors: Timothy Daly, Bruno P. Imbimbo

Institutions: Centre National de la Recherche Scientifique, Sorbonne Université, Facultad Latinoamericana de Ciencias Sociales Sede Argentina, Sciences, Normes, Démocratie, Chiesi (Italy)

Language: English

Topic: Alzheimer's disease research and treatments

Subfield: Physiology

Field: Medicine

Domain: Health Sciences

SDG: Good health and well-being

Open Access status: hybrid

Estimated APC paid: $3,740