Substance Abuse and Cognitive Decline: The Critical Role of Tau Protein as a Potential Biomarker
International Journal of Molecular Sciences August 7, 2025 Liliana Rebolledo-Pérez, Jorge Hernández‐bello, Alicia Martínez-ramos et al. 5 citations
Tau protein, essential for neuron stability, becomes toxic when hyperphosphorylated or cleaved, contributing to Alzheimer's disease. Evidence from experimental, clinical, and postmortem studies indicates that chronic substance use alters Tau dynamics in substance-specific ways. Alcohol and opioids promote Tau hyperphosphorylation and fragmentation via kinases like GSK-3β and CDK5 and proteases like caspase-3, leading to neuroinflammation. Stimulants and dissociatives disrupt insulin signaling and increase oxidative stress, exacerbating Tau pathology. Cannabinoids and psychedelics may protect by modulating kinase activity and reducing inflammation; psilocybin and harmine decrease Tau phosphorylation in animal models. Tau emerges as a convergent target in substance-related cognitive disorders, offering a biomarker and therapeutic target.