ApoE-calypse tau: ApoE–tau synergy in Alzheimer’s disease

Alzheimer's disease (AD), the most common cause of dementia, is characterized by the accumulation of amyloid-β (Aβ) in senile plaques and abnormally hyperphosphorylated tau proteins in neurofibrillary tangles. While much of the research has focused on Aβ, tau-mediated neurodegeneration is more closely associated with synaptic loss and cognitive decline in AD, emphasizing the need for a deeper understanding of tau pathology. In this context, the interaction between tau and APOE, particularly the main genetic risk factor for AD APOE ε4, remains underexplored. APOE encodes apolipoprotein E (apoE), a protein important in lipid metabolism. In addition to promoting Aβ deposition, emerging evidence suggests that APOE ε4 exacerbates tau-mediated neurodegeneration and tau-related pathology. This review consolidates current knowledge on the interplay between apoE and tau, highlighting its potential as a key factor in disease progression. Targeting the apoE-tau axis may offer promising therapeutic strategies to address the molecular mechanisms driving AD and primary tauopathies.