Mesencephalic astrocyte-derived neurotrophic factor (MANF), an endoplasmic reticulum (ER) stress-inducible protein, was initially identified as a member of the new family of neurotrophic factors and plays a cytoprotective role in Parkinson’s disease, Alzheimer’s disease, cerebral ischemia, and diabetes [22–25]. Here, MANF is linked to early-onset autosomal dominant Alzheimer disease.