Impaired BMP/TGF-β signaling was found in some neurodegenerative diseases including ALS, Huntington disease, hereditary spastic paraplegias, spinal muscular atrophy, spinobulbar muscular atrophy, and Alzheimer disease.23 Familial ALS and sporadic ALS also show reduced nuclear phosphorylated Smad (pSmad) levels and pSmad aggregates in cytoplasm.24 This evidence concerns the gene TGFB1 and early-onset autosomal dominant Alzheimer disease.