The mutations at the splice junction of exon 10 of tau lead to the selective deposition of the repetitive tau in neurons and glia. The pathological phenotype associated with mutations elsewhere in tau is less predictable with both typical neurofibrillary tangles (consisting of both 3 repeat and 4 repeat tau) and Pick bodies (consisting of 3 repeat tau) having been described. The presence of tau deposits within glia is also variable in families with mutations outside of exon 10. This disease is now informally designated FTDP-17T. FTD shows a linkage to the region of the tau locus on chromosome 17, but it is believed that there are two loci leading to FTD within megabases of each other on chromosome 17. The only other known autosomal dominant genetic cause of FTLD-tau is a hypomorphic mutation in VCP which is associated with a unique neuropathology called vacuolar tauopathy. FTD caused by FTLD-TDP43 has numerous genetic causes. Some cases are due to mutations in the GRN gene, also located on chromosome 17. Others are caused by hypomorphic VCP mutations, although these patients present with a complex picture of multisystem proteinopathy that can include amyotrophic lateral sclerosis, inclusion body myopathy, Pagets disease of bone, and FTD. The most recent addition to the list is a hexanucleotide repeat expansion in intron 1 of C9ORF72. Only one or two cases have been reported describing TARDBP (the TDP-43 gene) mutations in a clinically pure FTD (FTD without MND). Several other genes have been linked to this condition.
Currently, there is no cure for FTD, but there are treatments that help alleviate symptoms. Signs and symptoms
Frontotemporal dementia (FTD) is an early-onset disorder that mostly occurs before the age of 65, but can begin earlier, and in 20–25% of cases onset is later. It is the most common early presenting dementia.The International Classification of Diseases recognizes the disease as causative to disorder affecting mental and behavioural aspects of the human organism. Dissociation from family, extreme oniomania, vulgar speech characteristics, screaming, inability to control emotions, behavior, personality, and temperament are characteristic social display patterns. A gradual onset and progression of changes in behavior or language deficits are reported to have begun several years prior to presentation to a neurologist. Subtypes and related disorders
The main subtypes of frontotemporal dementia are behavioral variant FTD, semantic dementia, progressive nonfluent aphasia, and FTD associated with amyotrophic lateral sclerosis (FTD–ALS). Two distinct rare subtypes are neuronal intermediate filament inclusion disease, and basophilic inclusion body disease. Related disorders are corticobasal syndrome, and progressive supranuclear palsy. Behavioral variant frontotemporal dementia
Behavioral variant frontotemporal dementia (BvFTD) was previously known as Picks disease, and is the most common of the FTD types. BvFTD is diagnosed four times as often as the PPA variants. Behavior can change in BvFTD in either of two ways—it can change to being impulsive and disinhibited, acting in socially unacceptable ways; or it can change to being listless and apathetic.