In contrast, components reflecting microglial reactivity, astrocytic reactivity, and cytokine signalling were associated with longitudinal GM volume increases, with effects varying by AT stage.<h4>Conclusions</h4>In this large longitudinal sample of asymptomatic individuals, Aβ pathology emerged as the primary contributor to early neurodegeneration and cognitive decline, beyond the effects of tau pathophysiology and neuroaxonal injury. Here, MAPT is linked to Mental deterioration.