Frontotemporal Lobar Degeneration - Histology

Histology

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

• FTLD -tau; which is characterised by tau positive inclusions often referred to as Pick-bodies. Examples of FTLD-tau include; Pick's disease, corticobasal degeneration, progressive supranuclear palsy.
• FTLD-TDP43; which is characterised by ubiquitin and TDP-43 positive, tau negative, FUS negative inclusions. The pathological histology of this subtype is so diverse it is subdivided into four subtypes based on the detailed histological findings.

FTLD-TDP43 Type1 presents many long neuritic profiles found in the superficial cortical laminae, very few or no neuronal cytoplasmic inclusions, neuronal intranuclear inclusions or glial cytoplasmic inclusions. FTLD-TDP43 Type2 presents with lots of neuronal and glial cytoplasmic inclusions in both the upper (superficial) and lower (deep) cortical layers, and lower motor neurons. However neuronal intranuclear inclusions are rare or absent. FTLD-TDP43 Type3 presents with many small neurites and neuronal cytoplasmic inclusions in the upper (superficial) cortical layers. Bar-like neuronal intranuclear inclusions can also be seen they are fewer in number. This type is associated with C9ORF72 mutations (see next section). FTLD-TDP-43 Type4 presents with lots of neuronal intranuclear inclusions and dystrophic neurites, and an unusual absence of inclusions in the granual cell layer of the hippocampus. Type 4 is associated with VCP mutations.

• FTLD-FUS; which is characterised by FUS positive cytoplasmic inclusions, intra nuclear inclusions, and neuritic threads. All of which are present in the cortex, medulla, hippocampus, and motor cells of the spinal cord and XIIth cranial nerve.

• Dementia lacking distinctive histology (DLDH) is a rare and controversial entity. New analyses has allowed many cases previously described as DLDH to be reclassified into one of the positively-defined subgroups.