Selective functional, regional, and neuronal vulnerability in frontotemporal dementia

Purpose of reviewThe molecular neuroscience revolution has begun to rekindle interest in fundamental neuroanatomy. Blending these disciplines may prove critical to our understanding of neurodegenerative diseases, which target specific anatomical systems. Recent research on frontotemporal dementia highlights the potential value of these approaches. Recent findingsThe behavioral variant of frontotemporal dementia leads to progressive social–emotional processing deficits accompanied by anterior cingulate and frontal insular degeneration. These sites form a discrete human neural network and feature a class of layer 5b projection neurons, von Economo neurons, found only in large-brained, socially complex mammals. von Economo neurons have been shown to represent an early target in the behavioral variant of frontotemporal dementia but not in Alzheimer's disease. SummaryIntegrative approaches to selective vulnerability may help clarify neurodegenerative disease pathogenesis.