Frontotemporal Dementia - Pathology

Pathology

A number of case series have now been published looking at the pathological basis of frontotemporal dementia. As with other syndromes associated with frontotemporal lobar degeneration (FTLD), a number of different pathologies are associated with FTD:

• Tau pathology. Examples include Pick's disease, now also referred to as FTLD-tau, and other tau-positive pathology including FTDP-17, corticobasal degeneration, progressive supranuclear palsy. Approximately 50% of FTD cases will present with tau pathology at post-mortem.
• TDP-43 pathology. Previously described as dementia with ubiquitin positive, tau- and alpha-synuclein negative inclusions with and without motor neuron degeneration. FTLD-TDP43 accounts for approximately 40% of FTD(± MND).
• FUS pathology. Cases with underlying FUS pathology tend to present with behavioural variant FTD (bvFTD) but the correlation is by no means reliable enough to predict the post mortem pathology. FTLD-FUS represents only 5–10% of clinically diagnosed FTD.
• Dementia lacking distinctive histology (DLDH) is a rare entity and represents the remaining small percentage of FTD that cannot be positively diagnosed as any of the above at post-mortem.
• In rare cases, patients with clinical FTD were found to have changes consistent with Alzheimer's disease on autopsy
• Evidence suggests that FTD selectively impairs spindle neurons, a type of neuron which has only been found in the brains of humans, great apes, and whales.