Your search for: 'author:("Gambetti, Pierluigi")' has returned 4 results. (0.007s) Save search

Authors: Tabaton, Massimo | Gambetti, Pierluigi

Article Type: Research Article

Abstract: Researchers since the 1990s have predominantly focused on the amyloid hypothesis and the formation of amyloid fibrils as the culprit behind AD when we began working on soluble Aβ (sAβ). Unexpectedly, this work produced several novel findings. First, we observed that N-terminal truncated peptides are the major components of soluble and insoluble Aβ in AD; secondly, that all sAβ species belong to the 42 form and the sAβ x-40 species is virtually absent in AD parenchyma; thirdly, that Aβ42 in the soluble form is non-detectable by immunoblots in plaque-free, normal brains. The later observation that sAβ 42 species is present …in amyloid β protein precursor (AβPP) over-expressing brains of patients with Down syndrome in prenatal and early postnatal development argued that sAβ is present in brain in abnormal conditions and that its appearance seeds Aβ aggregation and accumulation. Although the sAβ we described in intact brain tissue appeared to match the soluble Aβ oligomers detected in cell media, which were subsequently shown to be the most toxic form of Aβ, our research has been virtually ignored by the Alzheimer field. It continues nevertheless. Recently we demonstrated that the sAβ species present in physiologically aging brains are different from those present in brains with sporadic AD as the latter form oligomers more quickly, are more toxic to neurons, and produce more severe membrane damage than the Aβ species associated with normal brain aging. Furthermore, in familial AD, the composition of soluble Aβ appears to dictate distinctive features of the disease phenotype introducing the notion of Aβ strains, a concept well established in prion diseases. Show more

DOI: 10.3233/JAD-2006-9S315

Citation: Journal of Alzheimer's Disease, vol. 9, no. s3, pp. 127-132, 2006

Authors: Gambetti, Pierluigi | Parchi, Piero | Capellari, Sabina | Russo, Claudio | Tabaton, Massimo | Teller, Jan K. | Chen, Shu G.

Article Type: Research Article

DOI: 10.3233/JAD-2001-3113

Citation: Journal of Alzheimer's Disease, vol. 3, no. 1, pp. 87-95, 2001

Authors: Vitali, Antonella | Piccini, Alessandra | Borghi, Roberta | Fornaro, Pantaleo | Siedlak, Sandra L. | Smith, Mark A. | Gambetti, Pierluigi | Ghetti, Bernardino | Tabaton, Massimo

Article Type: Research Article

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. Show more

Keywords: Alzheimer's disease, amyloid β-protein, FTDP-17, tau protein, tau pathology

DOI: 10.3233/JAD-2004-6106

Citation: Journal of Alzheimer's Disease, vol. 6, no. 1, pp. 45-51, 2004

Authors: Zaidi, Syed I.A. | Richardson, Sandra L. | Capellari, Sabina | Song, Li | Smith, Mark A. | Ghetti, Bernardino | Sy, Man-Sun | Gambetti, Pierluigi | Petersen, Robert B.

Article Type: Research Article

Abstract: Prion diseases are associated with the accumulation of a misfolded, protease resistant form of the prion protein, PrPres . In humans there are a variety of different prion related diseases that are sporadic, inherited, or acquired by infection. Gerstmann-Straussler-Sheinker syndrome (GSS) is an inherited prion disease in which PrPres accumulates as amorphous aggregates as well as in amyloid plaques. GSS has been associated with a variety of point mutations in the prion protein: 102, 105, 117, 131, 145, 187, 198, 202, 212, 217, and 232. The F198S mutation was discovered in a large Indiana kindred. Previous studies in vitro have …shown that the 198 mutation results in structural instability of the prion protein. In the current study, we demonstrate in a cell model that the F198S mutant protein can be folded properly in a cellular context, but is unable to refold to a native state after denaturation. Further, the F198S mutation significantly affects glycosylation of the mutant protein. Show more

DOI: 10.3233/JAD-2005-7209

Citation: Journal of Alzheimer's Disease, vol. 7, no. 2, pp. 159-171, 2005