New unexpected role for Wolfram Syndrome protein WFS1: a novel therapeutic target for Alzheimer′s disease?

Selective vulnerability of excitatory neurons in Alzheimer's disease (AD): AD is the most common form of dementia; however, the pathogenesis of AD is largely unknown. One of the characteristic features of AD is the formation of intracellular neurofibrillary tangles (NFTs). NFTs are abnormal accumulates of misfolded tau protein, which may eventually cause neuronal death and neurodegeneration (Jack et al., 2018). In the early stages of AD progression, not all neurons are equally vulnerable to tau aggregates. Previous studies have shown that large pyramidal neurons in the entorhinal cortex (EC) are specifically vulnerable to pathological tau accumulation (Fu et al., 2017). This selective vulnerability of excitatory neurons to tau pathology is one of the fundamental questions needed to be answered in AD research.