Coexisting adult polyglucosan body disease with frontotemporal lobar degeneration with transactivation response DNA-binding protein-43 (TDP-43)-positive neuronal inclusions

Abstract

Frontotemporal lobar degeneration with ubiquitin-positive inclusions (FTLD-U) is one of the most common pathological findings associated with the clinical FTLD syndromes. However, molecular characterization with genetic sequencing and protein expression techniques are recognizing many new subtypes for FTLDs. FTLDs are diverse and new nomenclature schemes have been proposed based on the molecular defects that are being discovered ( Mackenzie et al., 2010 , Acta Neuropathologica, 119, 1). Adult polyglucosan body disease (APBD) is a very rare disorder associated with systemic neurological signs and symptoms including progressive dementia with executive dysfunction and motor neuron disease. We report the clinical course of an individual with a clinical FTLD and the as yet unreported findings of coexistent APBD with FTLD-U and transactivation response DNA-binding protein-43 (TDP-43)-positive inclusions at autopsy (or more accurately, FTLD-TDP). It is unclear if these distinct findings are coincidental in this individual, or if pathogenic pathways may intersect to promote these coexisting pathologies.

Figure 1

A) Coronal gross brain specimen displaying enlarged ventricles, generalized atrophy, and temporal atrophy more prominent on the left (right side of figure), B) Low power photomicrograph of left frontal centrum semiovale with white matter pallor (H&E stain, original magnification 20×), C, D) High power photomicrographs of white matter with diffuse polyglucosan bodies and reactive astrocytosis (original magnification 200×, C – H&E stain, D – ubiquitin immunohistochemistry).

Figure 2

A) TDP-43 neuronal inclusions in frontal cortex (TDP-43 immunohistochemistry), B) Lens shaped or cat's eye inclusion in the caudate nucleus (ubiquitin immunohistochemistry). (magnification bar for both A and B – 10 um).