scholarly journals Evidence For and Against a Pathogenic Role of Reduced γ-Secretase Activity in Familial Alzheimer’s Disease

2016 ◽  
Vol 52 (3) ◽  
pp. 781-799 ◽  
Author(s):  
Tanya Jayne ◽  
Morgan Newman ◽  
Giuseppe Verdile ◽  
Greg Sutherland ◽  
Gerald Münch ◽  
...  
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Pathogenic Role ◽  
Familial Alzheimer’S Disease ◽  
Secretase Activity ◽  
Familial Alzheimer's Disease

scholarly journals Qualitative changes in human γ-secretase underlie familial Alzheimer’s disease

2015 ◽  
Vol 212 (12) ◽  
pp. 2003-2013 ◽  
Author(s):  
Maria Szaruga ◽  
Sarah Veugelen ◽  
Manasi Benurwar ◽  
Sam Lismont ◽  
Diego Sepulveda-Falla ◽  
...  
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Amyloid Β ◽  
Common Denominator ◽  
Activity Levels ◽  
Familial Alzheimer’S Disease ◽  
Secretase Activity ◽  
Constant Feature ◽  
Familial Alzheimer's Disease ◽  
And Control

Presenilin (PSEN) pathogenic mutations cause familial Alzheimer’s disease (AD [FAD]) in an autosomal-dominant manner. The extent to which the healthy and diseased alleles influence each other to cause neurodegeneration remains unclear. In this study, we assessed γ-secretase activity in brain samples from 15 nondemented subjects, 22 FAD patients harboring nine different mutations in PSEN1, and 11 sporadic AD (SAD) patients. FAD and control brain samples had similar overall γ-secretase activity levels, and therefore, loss of overall (endopeptidase) γ-secretase function cannot be an essential part of the pathogenic mechanism. In contrast, impaired carboxypeptidase-like activity (γ-secretase dysfunction) is a constant feature in all FAD brains. Significantly, we demonstrate that pharmacological activation of the carboxypeptidase-like γ-secretase activity with γ-secretase modulators alleviates the mutant PSEN pathogenic effects. Most SAD cases display normal endo- and carboxypeptidase-like γ-secretase activities. However and interestingly, a few SAD patient samples display γ-secretase dysfunction, suggesting that γ-secretase may play a role in some SAD cases. In conclusion, our study highlights qualitative shifts in amyloid-β (Aβ) profiles as the common denominator in FAD and supports a model in which the healthy allele contributes with normal Aβ products and the diseased allele generates longer aggregation-prone peptides that act as seeds inducing toxic amyloid conformations.

scholarly journals Neuroprotective Role of Trans-Resveratrol in a Murine Model of Familial Alzheimer's Disease

2014 ◽  
Vol 42 (4) ◽  
pp. 1209-1220 ◽  
Author(s):  
David Porquet ◽  
Christian Griñán-Ferré ◽  
Isidre Ferrer ◽  
Antoni Camins ◽  
Coral Sanfeliu ◽  
...  
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Murine Model ◽  
Familial Alzheimer’S Disease ◽  
Familial Alzheimer's Disease

Evaluation of the Role of JNK1 in the Hippocampus in an Experimental Model of Familial Alzheimer’s Disease

2015 ◽  
Vol 53 (9) ◽  
pp. 6183-6193 ◽  
Author(s):  
Dmitry Petrov ◽  
Melani Luque ◽  
Ignacio Pedrós ◽  
Miren Ettcheto ◽  
Sonia Abad ◽  
...  
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Experimental Model ◽  
Familial Alzheimer’S Disease ◽  
Familial Alzheimer's Disease

scholarly journals Possible Role of STIM1 Sensor Signal in Memory Loss Connected with Familial Alzheimer's Disease

2015 ◽  
Vol 108 (2) ◽  
pp. 588a
Author(s):  
Maria Ryazantseva ◽  
Ksenia Skobeleva ◽  
Anna Goncharova ◽  
Nikolai Kamyshev ◽  
Elena Kaznacheyeva
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Memory Loss ◽  
Sensor Signal ◽  
Familial Alzheimer’S Disease ◽  
Familial Alzheimer's Disease
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