Pathological Hallmarks, Clinical Parallels, and Value for Drug Testing in Alzheimer's Disease of the APP[V717I] London Transgenic Mouse Model.
The APP[V717I] London (APP-Ld) mouse model recapitulates important pathological and clinical hallmarks of Alzheimer's disease (AD) and is therefore a valuable paradigm for evaluating therapeutic candidates. Historically, both the parenchymal and vascular amyloid deposits, and more recently, truncated and pyroglutamate-modified Abeta(3(pE)-42) species, are perceived as important hallmarks of AD-pathology. Late stage symptoms are preceded by robust deficits in orientation and memory that correlate in time with Abeta oligomerization and GSK3β-mediated phosphorylation of endogenous murine Tau, all markers that have gained considerable interest during the last decade. Clinical parallels with AD patients and the value of the APP-Ld transgenic mouse model for preclinical in vivo testing of candidate drugs are discussed.
Tanghe
An
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reMYND NV, Gaston Geenslaan 1, 3001 Heverlee-Leuven, Belgium.
Termont
Annelies
A
Merchiers
Pascal
P
Schilling
Stephan
S
Demuth
Hans-Ulrich
HU
Scrocchi
Louise
L
Van Leuven
Fred
F
Griffioen
Gerard
G
Van Dooren
Tom
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