Deletion of Murine APP Aggravates Tau and Amyloid Pathologies in the 5xFADXTg30 Alzheimer's Disease Model

被引：1

作者：

Ando, Kunie ^{[1
]}

Kosa, Andreea-Claudia ^{[1
]}

Mehadji, Yasmina ^{[1
]}

Lasri, Hinde ^{[1
]}

Lopez-Gutierrez, Lidia ^{[1
]}

Quintanilla-Sanchez, Carolina ^{[1
]}

Aydin, Emmanuel ^{[1
]}

Doeraene, Emilie ^{[1
]}

Wathelet-Depauw, Alain ^{[1
]}

Nagaraj, Siranjeevi ^{[1
]}

Brion, Jean-Pierre ^{[1
]}

Leroy, Karelle ^{[1
]}

机构：

[1] Univ Libre Bruxelles, ULB Neurosci Inst UNI, ULB Ctr Diabet Res UCDR, Alzheimer & Other Tauopathies Res Grp,Fac Med, 808 Route Lennik,Bldg GE, B-1070 Brussels, Belgium

来源：

BIOMOLECULES | 2025年 / 15卷 / 02期

关键词：

Alzheimer's disease; amyloid precursor protein; amyloid beta; pTau; gliosis; PAIRED HELICAL FILAMENTS; PRECURSOR-PROTEIN; NEUROFIBRILLARY TANGLES; ALPHA-SECRETASE; TRANSGENIC MOUSE; MONOCLONAL-ANTIBODY; BETA-SECRETASE; MICE; GENE; PHOSPHORYLATION;

D O I：

10.3390/biom15020159

中图分类号：

Q5 [生物化学]; Q7 [分子生物学];

学科分类号：

071010 ; 081704 ;

摘要：

Alzheimer's disease is characterized by two key neuropathological lesions: amyloid plaques composed of amyloid beta and neurofibrillary tangles formed by hyperphosphorylated tau. Amyloid beta is produced through successive cleavages of amyloid precursor protein (APP) via the amyloidogenic pathway. While increasing evidence suggests that APP plays critical roles in neuronal function and that its proteolytic derivative, sAPP alpha, has neurotrophic effects, the impact of APP deletion on both amyloid and tau pathologies remains poorly understood. Here, we introduce a novel transgenic mouse model, 5xFADxTg30XAPP-/-, in which murine APP is deleted in the presence of both amyloid and tau pathologies. Using this innovative model, we demonstrate for the first time that deletion of APP exacerbates tau aggregation, amyloid deposition, and gliosis compared to control 5xFADxTg30 mice. This study provides the first in vivo evidence that APP deletion has profound and detrimental effects on both amyloid and tau pathologies in a transgenic model of Alzheimer's disease, highlighting the previously unappreciated role of APP in the regulation of these neurodegenerative processes.

引用

页数：16

共 52 条

[21] ALZHEIMERS-DISEASE - INITIAL REPORT OF THE PURIFICATION AND CHARACTERIZATION OF A NOVEL CEREBROVASCULAR AMYLOID PROTEIN [J].