These include CYLD, OPTN, SQSTM1 and TBK1. These genes have been implicated in the autophagy pathway. No genetic causes of FUS pathology in FTD have yet been reported. Pathology
There are three main histological subtypes found at post-mortem: FTLD-tau, FTLD-TDP, and FTLD-FUS. In rare cases, patients with clinical FTD were found to have changes consistent with Alzheimers disease on autopsy. The most severe brain atrophy appears to be associated with behavioral variant FTD, and corticobasal degeneration.With regard to the genetic defects that have been found, repeat expansion in the C9orf72 gene is considered a major contribution to frontotemporal lobar degeneration, although defects in the GRN and MAPT genes are also associated with it. Diagnosis
FTD is traditionally difficult to diagnose owing to the diverse nature of the associated symptoms. Signs and symptoms are classified into three groups based on the affected functions of the frontal and temporal lobes: These are behavioural variant frontotemporal dementia, semantic dementia, and progressive nonfluent aphasia. An overlap between symptoms can occur as the disease progresses and spreads through the brain regions. Structural MRI scans often reveal frontal lobe and/or anterior temporal lobe atrophy but in early cases the scan may seem normal. Atrophy can be either bilateral or asymmetric. Registration of images at different points of time (e.g., one year apart) can show evidence of atrophy that otherwise (at individual time points) may be reported as normal.
About 12–13% of people with bvFTD develop motor neuron disease.The Pick bodies in behavioral variant FTD are spherical inclusion bodies found in the cytoplasm of affected cells. They consist of tau fibrils as a major component together with a number of other protein products including ubiquitin and tubulin. Semantic dementia
Semantic dementia (SD) is characterized by the loss of semantic understanding, resulting in impaired word comprehension. However, speech remains fluent and grammatical. Progressive nonfluent aphasia
Progressive nonfluent aphasia (PNFA) is characterized by progressive difficulties in speech production. Neuronal intermediate filament inclusion disease
Neuronal intermediate filament inclusion disease (NIFID) is a rare distinct variant. The inclusion bodies that are present in NIFID are cytoplasmic and made up of type IV intermediate filaments. NIFID has an early age of onset between 23 and 56. Symptoms can include behavioural, and personality changes, memory and cognitive impairments, language difficulties, motor weakness, and extrapyramidal symptoms. NIFID is one of the FTLD-FUS proteopathies. Imaging commonly shows atrophy in the frontotemporal region, and in part of the striatum in the basal ganglia. Post-mortem studies show a marked reduction in the caudate nucleus of the striatum; frontal temporal gyri are narrowed with widened intervening sulci, and the lateral ventricles are enlarged. Basophilic inclusion body disease
Another rare FTD variant, also a FTLD-FUS proteopathy, is basophilic inclusion body disease (BIBD). Other characteristics
In later stages of FTD, the clinical phenotypes may overlap. People with FTD tend to struggle with binge eating and compulsive behaviors.