Accelerated amyloid deposition, neurofibrillary degeneration and neuronal loss in double mutant APP/tau transgenic mice.
Even though the idea that amyloid beta peptide accumulation is the primary event in the pathogenesis of Alzheimer's disease has become the leading hypothesis, the causal link between aberrant amyloid precursor protein processing and tau alterations in this type of dementia remains controversial. We further investigated the role of beta-amyloid production/deposition in tau pathology and neuronal cell death in the mouse brain by crossing Tg2576 and VLW lines expressing human mutant amyloid precursor protein and human mutant tau, respectively. The resulting double transgenic mice showed enhanced amyloid deposition accompanied by neurofibrillary degeneration and overt neuronal loss in selectively vulnerable brain limbic areas. These findings challenge the idea that tau pathology in Alzheimer's disease is merely a downstream effect of amyloid production/deposition and suggest that reciprocal interactions between beta-amyloid and tau alterations may take place in vivo.
Ribé
Elena M
EM
Departmento de Neurología, Universidad de Navarra, Pamplona, Navarra, Spain.
Pérez
Mar
M
Puig
Berta
B
Gich
Ignasi
I
Lim
Filip
F
Cuadrado
Mar
M
Sesma
Teresa
T
Catena
Silvia
S
Sánchez
Belén
B
Nieto
María
M
Gómez-Ramos
Pilar
P
Morán
M Asunción
MA
Cabodevilla
Felipe
F
Samaranch
Lluis
L
Ortiz
Lourdes
L
Pérez
Alberto
A
Ferrer
Isidro
I
Avila
Jesús
J
Gómez-Isla
Teresa
T
D000544:Alzheimer Disease / Q000235:genetics / Q000378:metabolism* / Q000503:physiopathology; D016229:Amyloid beta-Peptides / Q000096:biosynthesis; D016564:Amyloid beta-Protein Precursor / Q000235:genetics*; D000818:Animals; D001921:Brain / Q000378:metabolism / Q000473:pathology / Q000503:physiopathology; D016923:Cell Death / Q000235:genetics; D004195:Disease Models, Animal; D005260:Female; D006801:Humans; D008297:Male; D051379:Mice; D018345:Mice, Knockout; D008822:Mice, Transgenic; D009154:Mutation / Q000235:genetics; D009410:Nerve Degeneration / Q000235:genetics / Q000378:metabolism* / Q000503:physiopathology; D016874:Neurofibrillary Tangles / Q000235:genetics / Q000378:metabolism*; D009474:Neurons / Q000378:metabolism / Q000473:pathology; D058225:Plaque, Amyloid / Q000235:genetics / Q000378:metabolism*; D016875:tau Proteins / Q000235:genetics*
D016229:Amyloid beta-Peptides; D016564:Amyloid beta-Protein Precursor; D016875:tau Proteins