Pick's disease and other tauopathies (FTLD-T)

Pathologically, two major types of changes are observed in FTLD: gross morphologic atrophy in the frontal and anterior temporal lobes, and microscopic changes, including any or all of the following: gliosis, inclusion bodies, swollen neurons, and microvacuolation. Increasingly, the focus of research is upon whether the inclusions within neurons or glia consist of tau or ubiquitin-TDP-43.

Gross Anatomical Changes

In FTLD, a mild to severe decrease in overall brain weight and atrophy of the frontal and temporal lobes occur. Thinning of the cortical ribbon and discoloration of white matter may also be present. In other cases, atrophy may extend into the parietal lobes, amygdala, hippocampus, thalamus and basal ganglia (head of the caudate nucleus) (Mann and South, 1993). Ventricular enlargement is also be observed, as well as pallor of the substantia nigra, atrophy of the anterior nerve roots and discoloration of the lateral funiculus in the spinal cord.

Microscopic Findings

Much of the gross atrophy seen at pathology results from synapse loss, dendritic atrophy and neuron loss often accentuated in superficial layers.

Remaining neurons show two distinctive histologic features: swelling (called "ballooned" or "Pick cell") and an inclusion within the perikaryon, most often in layer II (Pick body). Pick bodies are usually found in limbic (greatest concentration is in the amygdala and hippocampus, including the dentate gyrus), paralimbic, and ventral temporal lobe cortex, but may also be seen in anterior frontal and dorsal temporal lobes. They are rarely found elsewhere in the brain. Pick bodies are composed of randomly arranged filaments of the tau protein.

Despite the origins of the FTLD classification, only a minority of patients diagnosed with FTLD will show the classical Pick pattern at autopsy. Furthermore, even in patients with tau inclusions, the majority will not show the classical Pick body that stains positive with silver stains (argyrophilic).