In this review, we explore a key common pathological mechanism, i.e., the loss of neuroprotective factors (i.e., the Brain Derived Neurotrophic Factor, progranulin and cystatin C) across the three major neurodegenerative diseases leading to dementia: Alzheimer's disease (AD), Frontotemporal dementia (FTD) and Lewy body dementia (LBD). Here, GRN is linked to early-onset autosomal dominant Alzheimer disease.