Cellular inclusions

Unlike Alzheimer's disease, the brain tissue of people with FTD does not show plaques and rarely shows tangles. Brain tissue from patients with FTD often show cellular inclusions - clumps of protein that build up within brain cells (neurons). The classical cellular inclusion, named a “Pick body” nearly one-hundred years ago, stains positively for a protein called tau. Tau is a protein involved in stabilizing microtubules, proteins that support the structure and shape of neurons. About 40% of people with FTD have these tau-positive inclusions. Frontotemporal dementia was once known as "Pick's disease."

A second type of cellular inclusion found in people with frontotemporal dementia is made up of two other proteins called ubiquitin and TDP-43. Ubiquitin is a protein that is involved with clearing waste products from the cell, while TDP-43 is a protein involved with making proteins from the instructions contained in DNA. Nearly all patients with FTD and amyotrophic lateral sclerosis (ALS), and most patients with semantic dementia, show these ubiquitin-TDP-43 inclusions.

The term "frontotemporal lobar degeneration" (FTLD) is used to describe the specific pathological diseases that result in FTD syndromes. These pathological diseases are distinguished by the specific proteins found within the neuronal inclusions. Most FTLD subtypes are either

1. FTLD-tau, which includes Pick’s disease, corticobasal degeneration (CBD) and progressive supranuclear palsy (PSP), all of which show tau-containing inclusions or
2. FTLD-TDP, which includes several subtypes in which TDP-43 containing inclusions are seen.