Introduction

Unlike Alzheimer's disease, FTLD doesn't show amyloid plaques and neurofibrillary tangles. Instead, FTLD brains show severe atrophy and specific neuronal inclusions. The brain tissue of approximately 40% of people with FTLD shows tau inclusions or “Pick bodies”. The other inclusions seen more frequently than tau are made of the protein ubiquitin, normally involved in clearing waste products from cell and TDP-43 a protein involved with DNA modulation.

Tau is a neuronal protein that binds to microtubules and is thought to be involved in the stabilization of the neuron's three-dimensional structure. In the normal adult human brain, tau is a soluble protein that is expressed as six major protein isoforms generated by alternative splicing of the tau gene. The tau gene is found on chromosome 17q21 and more than 50 different mutations have been associated with hereditary FTD. Tau mutations can reduce the binding affinity of tau for microtubules or increase tau accumulation, both of which lead to FTD and Parkinsonism linked to chromosome 17 (FTDP-17). Most patients with tau gene mutations develop an autosomal dominantly inherited syndrome with features of FTD. However, a large pathological and clinical heterogeneity is observed both among and within FTDP-17 families carrying the same mutation and some manifest with a corticobasal or progressive supranuclear palsy syndrome. No tau mutations have so far been reported in cases with classical AD.