Affiliations: [a] Department of Neurological Sciences, Psychiatry and Genetics, University of Genova, Italy | [b] Institute of Pathology, Case Western Reserve University, Cleveland, OH, USA | [c] Department of Neuropathology and Laboratory Medicine, Indiana University School of Medicine, Indianapolis, IN, USA
Correspondence:
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Corresponding author: Dr. Massimo Tabaton, Department of Neurological Sciences, Ophthalmology, and Genetics, University of Genova, Via De Toni 5, 16132 Genova, Italy. Tel.: +39 010 3537064; Fax: +39 010 3538639; E-mail: mtabaton@neurologia.unige.it.
Abstract: The relationship between senile plaques and neurofibrillary tangles, the main pathologic lesions of Alzheimer's disease, is not completely understood. We addressed this issue examining the type and amount of amyloid β-protein (Aβ) associated with the soluble and insoluble tissue fractions in the frontal cortex of 8 cases with frontotemporal dementia with parkinsonism caused by mutations of the Tau gene (FTDP-17), in which the intracellular accumulation of polymerised tau is definitely the primary cause of neurodegeneration. As control, we examined 7 cases with frontotemporal dementia lacking distinctive histopathology (DLDH) as well as 8 pathologically normal subjects. In all cases the presence of Aβ deposits was ruled out using immunocytochemistry on sections adjacent to those used for biochemical analysis. ELISA analysis showed a 2.7 and 2.1 fold (p < 0.01) increase of soluble Aβ42 and Aβ40 in FTDP-17, compared to normal and DLDH brains, both of which had comparable levels of Aβ species. Furthermore, the immunoreactivity of the intracellular Aβ42 was significantly increased in cortical neurons of subjects affected with FTDP-17. The results demonstrate that the aggregation of tau protein produces an accumulation of Aβ, which, however, does not reach the critical concentration needed for Aβplaques formation.
Keywords: Alzheimer's disease, amyloid β-protein, FTDP-17, tau protein, tau pathology
