Collectively, these findings suggest that αSyn co-pathology, as detected via CSF-based αSyn SAAs, is associated with an acceleration of Aβ-induced tau pathophysiology across the AD spectrum ensuing faster cognitive decline, overall positioning αSyn as a significant modulator of tauopathy in the context of Aβ pathology, as well as clinical disease progression in AD. The gene discussed is PCSK1N; the disease is Alzheimer disease.