Frontotemporal lobar degeneration

Frontotemporal lobar degeneration (FTLD) is a pathological process that occurs in frontotemporal dementia. It is characterized by atrophy in the frontal lobe and temporal lobe of the brain, with sparing of the parietal and occipital lobes.

Common proteinopathies that are found in FTLD include the accumulation of tau proteins and TAR DNA-binding protein 43 (TDP-43). Mutations in the C9orf72 gene have been established as a major genetic contribution of FTLD, although defects in the granulin (GRN) and microtubule-associated proteins (MAPs) are also associated with it.

Classification

There are 3 main histological subtypes found at post-mortem:

FTLD-tau is characterised by tau positive inclusion bodies often referred to as Pick-bodies. Examples of FTLD-tau include; Pick's disease, corticobasal degeneration, progressive supranuclear palsy.

FTLD-TDP (or FTLD-U ) is characterised by ubiquitin and TDP-43 positive, tau negative, FUS negative inclusion bodies. The pathological histology of this subtype is so diverse it is subdivided into four subtypes based on the detailed histological findings:

Type A presents with many small neurites and neuronal cytoplasmic inclusion bodies in the upper (superficial) cortical layers. Bar-like neuronal intranuclear inclusions can also be seen they are fewer in number.

Type B presents with many neuronal and glial cytoplasmic inclusions in both the upper (superficial) and lower (deep) cortical layers, and lower motor neurons.