Author:

Keywords:

Science & Technology, Life Sciences & Biomedicine, Biochemistry & Molecular Biology, Cell Biology, Alzheimer's disease, amyloid precursor protein, amyloid beta peptide, App knock-in, APP transgenic, AMYLOID-PRECURSOR-PROTEIN, HEREDITARY CEREBRAL-HEMORRHAGE, GENE-TARGETED MICE, TRANSGENIC MICE, A-BETA, PLAQUE-FORMATION, NEURONAL-ACTIVITY, MEMORY DEFICITS, NEURODEGENERATIVE DISEASES, INTRACELLULAR DOMAIN, App knock‐in, amyloid β peptide, Alzheimer Disease, Amyloid beta-Protein Precursor, Animals, Disease Models, Animal, Humans, 06 Biological Sciences, 08 Information and Computing Sciences, 11 Medical and Health Sciences, Developmental Biology, 31 Biological sciences, 32 Biomedical and clinical sciences

Abstract:

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-generation 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 unrelated to AD Second-generation mouse models contain humanized sequences and clinical mutations in the endogenous mouse App gene. These mice show Aβ accumulation without phenotypes related to overexpression but are not yet a clinical recapitulation of human AD In this review, we evaluate different APP mouse models of AD, and review recent studies using the second-generation mice. We advise AD researchers to consider the comparative strengths and limitations of each model against the scientific and therapeutic goal of a prospective preclinical study.