Mild stretch injury modeling mild TBI in human iPSC-derived neurons triggered amyloidogenic processing of APP, disrupting axonal transport and leading to accumulation of amyloid-related components associated with Alzheimer’s disease. Pharmacological inhibition of APP cleavage, as well as expression of the Alzheimer’s disease-protective A673T variant, prevented these stretch-induced transport defects, suggesting a potential strategy to reduce Alzheimer’s disease risk following mTBI. The gene discussed is APP; the disease is early-onset autosomal dominant Alzheimer disease.