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 AO plaques formation.
| Original language | English |
|---|---|
| Pages (from-to) | 45-51 |
| Number of pages | 7 |
| Journal | Journal of Alzheimer's Disease |
| Volume | 6 |
| Issue number | 1 |
| State | Published - Feb 2004 |
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Keywords
- Alzheimer's disease
- Amyloid β-protein
- FTDP-17
- Tau pathology
- Tau protein
ASJC Scopus subject areas
- Neuropsychology and Physiological Psychology
Cite this
Soluble amyloid β-protein is increased in frontotemporal dementia with tau gene mutations. / Vitali, Antonella; Piccini, Alessandra; Borghi, Roberta; Fornaro, Pantaleo; Siedlak, Sandra L.; Smith, Mark A.; Gambetti, Pierluigi; Ghetti, Bernardino; Tabaton, Massimo.
In: Journal of Alzheimer's Disease, Vol. 6, No. 1, 02.2004, p. 45-51.Research output: Contribution to journal › Article
}
TY - JOUR
T1 - Soluble amyloid β-protein is increased in frontotemporal dementia with tau gene mutations
AU - Vitali, Antonella
AU - Piccini, Alessandra
AU - Borghi, Roberta
AU - Fornaro, Pantaleo
AU - Siedlak, Sandra L.
AU - Smith, Mark A.
AU - Gambetti, Pierluigi
AU - Ghetti, Bernardino
AU - Tabaton, Massimo
PY - 2004/2
Y1 - 2004/2
N2 - 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 AO plaques formation.
AB - 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 AO plaques formation.
KW - Alzheimer's disease
KW - Amyloid β-protein
KW - FTDP-17
KW - Tau pathology
KW - Tau protein
UR - http://www.scopus.com/inward/record.url?scp=1842532341&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=1842532341&partnerID=8YFLogxK
M3 - Article
C2 - 15004327
AN - SCOPUS:1842532341
VL - 6
SP - 45
EP - 51
JO - Journal of Alzheimer's Disease
JF - Journal of Alzheimer's Disease
SN - 1387-2877
IS - 1
ER -