Soluble amyloid beta-protein is increased in frontotemporal dementia with tau gene mutations.
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 beta-protein (Abeta) 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 Abeta 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 Abeta42 and Abeta40 in FTDP-17, compared to normal and DLDH brains, both of which had comparable levels of Abeta species. Furthermore, the immunoreactivity of the intracellular Abeta42 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 Abeta, which, however, does not reach the critical concentration needed for Abetaplaques formation.
Department of Neurological Sciences, Psychiatry and Genetics, University of Genova, Italy.
Antonella
A
Vitali
Alessandra
A
Piccini
Roberta
R
Borghi
Pantaleo
P
Fornaro
Sandra L
SL
Siedlak
Mark A
MA
Smith
Pierluigi
P
Gambetti
Bernardino
B
Ghetti
Massimo
M
Tabaton
D000368:Aged; D000544:Alzheimer Disease / Q000235:genetics / Q000473:pathology; D016229:Amyloid beta-Peptides / Q000032:analysis*; D001921:Brain / Q000473:pathology*; D003704:Dementia / Q000235:genetics* / Q000473:pathology; D005091:Exons / Q000235:genetics*; D005260:Female; D005625:Frontal Lobe / Q000473:pathology; D015870:Gene Expression; D006801:Humans; D007124:Immunoenzyme Techniques; D008297:Male; D008869:Microtubule-Associated Proteins / Q000235:genetics*; D008875:Middle Aged; D009154:Mutation / Q000235:genetics*; D009419:Nerve Tissue Proteins / Q000235:genetics*; D016874:Neurofibrillary Tangles / Q000235:genetics / Q000473:pathology; D058225:Plaque, Amyloid / Q000235:genetics / Q000473:pathology; D012016:Reference Values; D024801:Tauopathies / Q000235:genetics* / Q000473:pathology; D013702:Temporal Lobe / Q000473:pathology; D016875:tau Proteins
D016229:Amyloid beta-Peptides; C054369:MAPT protein, human; D008869:Microtubule-Associated Proteins; D009419:Nerve Tissue Proteins; D016875:tau Proteins