Transgenic Mouse Models of Alzheimer’s Disease: An Integrative Analysis
, Juan Jose Fernandez-Valenzuela 1,2, Cristina Nuñez-Diaz 1,2, Laura Caceres-Palomo 1,2, Laura Vegas-Gomez 1,2, Elisabeth Sanchez-Mejias 1,2, Laura Trujillo-Estrada 1,2, Juan Antonio Garcia-Leon 1,2, Ines Moreno-Gonzalez 1,2,4, Marisa Vizuete 2,5, Javier Vitorica 2,5, David Baglietto-Vargas 1,2,* and Antonia Gutierrez 1,2,*
Round 1
Reviewer 1 Report
Alzheimer disease (AD) pathology is characterized by cerebral plaques containing aggregates of various amyloid-β (Aβ) peptides derived from amyloid precursor protein (APP), as well as by neurofibrillary tangles (NFTs) containing hyperphosphorylated and aggregated tau. Animal models of human diseases that accurately recapitulate clinical pathology are indispensable for understanding molecular mechanisms and advancing preclinical studies. The Alzheimer’s disease (AD) research community has historically used first-genera- tion transgenic (Tg) mouse models that overexpress proteins linked to familial AD (FAD), mutant amyloid precursor protein (APP), or APP and presenilin (PS). These mice exhibit AD pathology, but the overexpression paradigm may cause additional phenotypes unre- lated to AD. In this review, they provide a comprehensive overview about the major pathological elements of human AD (plaques, tauopathy, synaptic damage, neuronal death, neuroinflammation and glial dysfunction), discuss the knowledge that available mouse models have provided about the mechanisms underlying human disease. Moreover, they highlight the pros and cons of current models, and the revolution offered by the concomitant use of transgenic mice and omics technologies that may lead to a more rapid improvement of the present modeling battery.it's great job! It could be published on IJMS. Mini reversion: to check spelling and grammar.
Reviewer 2 Report
The review is devoted to transgenic mouse models of Alzheimer’s disease.
Introductory section has a brief description of the development of murine models of this pathology. The addition of some general characteristics of Alzheimer’s disease in humans would benefit the paper.
The second chapter is devoted to APP-based models of Alzheimer’s pathology in mice, starting from monogenic to biogenic models (combining both APP and presenilin mutations). Different morphological types of amyloid plaques are discussed as well as prion-like properties of A-beta amyloid. Further directions for the development of APP-based models are mentioned.
The third section of the review includes the information about the involvement of Tau aggregation in Alzheimer’s disease pathology, murine models of Tau-related pathology, and future prospectives of the development of these models.
The fourth chapter describes models of synaptic dysfunction, and neurodegeneration, also important aspects of Alzheimer’s disease pathology.
Microglial response in transgenic mice models of Alzheimer’s disease are reviewed in the fifth chapter with the description of findings done with the help of these models.
The sixth chapter describes the role of astrocytes for Alzheimer’s disease pathogenicity in the context of mice models used.
Oligodendrocytes role in Alzheimer’s disease found using murine models is reviewed in chapter seven.
Chapter eight contains the information about transcriptomic, and proteomic profiling of the above mentioned mice models.
This paper is quite detailed, and well written. The authors express balanced opinions on subjects in each section, and provide their opinions on directions of future research. Despite the presence of large amounts of reviews devoted to murine models of Alzheimer’s disease, this one provides a quite detailed analysis of the application of these models to study different aspects of this disease with description of limitations, and future experiments.
Minor note:
The list of abbreviations used would benefit the paper.
The review can be accepted for a publication.
