Hyperphosphorylated tau deposition parallels prion protein burden in a case of Gerstmann-Sträussler-Scheinker syndrome P102L mutation complicated with dementia

Abstract.

Hyperphosphorylated tau (p-tau) deposition has been documented in a limited population of patients with Gerstmann-Sträussler-Scheinker syndrome (GSS) with particular point mutations of the prion protein (PrP) gene. Although its pathogenesis is only poorly understood, p-tau in GSS is known to be identical to that in Alzheimer's disease (AD). We conducted immunohistochemical and quantitative image studies on the brain from a 44-year-old man with a 7-year history of dementia, diagnosed as having GSS with a point mutation of the PrP gene at codon 102 (GSS102), the commonest mutation in GSS. Severe spongiform degeneration and numerous PrP plaques were disclosed in the cerebral cortices and hippocampus, consistent with the diagnosis. However, rarely described in GSS102, prominent p-tau deposits as pretangles, neurofibrillary tangles and degenerating neurites were demonstrated adjacent to or around PrP plaques. β-Amyloid protein (Aβ) plaques were generally sparse and appeared invariably to be of a diffuse type. Double-labeling immunohistochemistry yielded co-localization of p-tau with PrP but not with Aβ. Most PrP plaques did not contain Aβ. These results excluded a diagnosis of concomitant AD. Quantitative analysis on a fractional area density of immunoreactive pixels demonstrated that burdens of PrP and p-tau but not Aβ were significantly correlated. These results suggest that p-tau deposition in this GSS102 is secondarily induced by PrP but not by Aβ (secondary tauopathy). Our study also suggests that p-tau deposition might be a more common phenomenon in long-standing GSS.