Rodent Models of Amyloid-Beta Feature of Alzheimer’s Disease: Development and Potential Treatment Implications

Abstract

Alzheimer's disease (AD) is the most common neurodegenerative disorder worldwide and causes severe financial and social burdens. Despite much research on the pathogenesis of AD, the neuropathological mechanisms remain obscure and current treatments have proven ineffective. In the past decades, transgenic rodent models have been used to try to unravel this disease, which is crucial for early diagnosis and the assessment of disease-modifying compounds. In this review, we focus on transgenic rodent models used to study amyloidbeta pathology in AD. We also discuss their possible use as promising tools for AD research. There is still no effective treatment for AD and the development of potent therapeutics are urgently needed. Many molecular pathways are susceptible to AD, ranging from neuroinflammation, immune response, and neuroplasticity to neurotrophic factors. Studying these pathways may shed light on AD pathophysiology as well as provide potential targets for the development of more effective treatments. This review discusses the advantages and limitations of these models and their potential therapeutic implications for AD.

Interdisciplinary Research in Alzheimer’s Disease and the Roles International Societies Can Play

“…The combination of pathological and clinical features, however, does not overcome the issue of defining the disease—defining a “disease” requires identification of the causes [ 15 ]. It has long been thought that AD is caused by the deposition of amyloid-β [ 3 , 4 ]. However, amyloid-β can be found in healthy older subjects [ 16 , 17 ], and there seems to be little to no correlation between amyloid load and the degree of cognitive decline in AD patients [ 18 , 19 ].…”

“…Other markers like tau and neurofibrillary tangles correlate better to cognitive decline in AD patients, yet this still does not establish a causative role, and may simply reflect a pathological feature of another causative process [ 15 ]. This lack of understanding of the causes of AD brings difficulties in itself, yet it is further compounded by the fact that it prevents the development of good experimental models [ 3 , 4 ]. Transgenic mice are one of the most widely used models in AD, and their use has been extensively discussed by Drummond and Wisniewski [ 20 ], yet they and others have noted issues in the lack of consistency of these experimental models or their lack of relevance (e.g., dependence on familial AD mutations but most cases tend to be sporadic).…”

“…The number of people with dementia is expected to more than triple by 2050, which will inevitably have enormous social and economic costs [ 2 ]. The experimental research in AD has been highly skewed in favor of Amyloid Cascade Hypothesis and the use of transgenic AD models [ 3 , 4 ]. At the same time a huge body of epidemiological data on various metabolic and environmental risk factors of AD has been somewhat ignored to develop suitable models or to formulate new treatment strategies for AD [ 5 ].…”

Therapeutic potential of neurogenesis and melatonin regulation in Alzheimer's disease

“…One of the most well-known and extensively researched pathologies is the accumulation of amyloid-beta plaques. 32 Amyloid-beta peptides are produced via the proteolytic processing of transmembrane APP by βand γ-secretases. 33 The accumulation of amyloid-beta peptides was found to suppress the proliferation of neural stem/progenitor cells and neuronal differentiation in various AD mouse AD, Alzheimer's disease; Aβ, amyloid beta; APP, amyloid precursor protein; PDGF, platelet-derived growth factor; PHF1, paired helical filament 1; PS1, presenilin-1.…”

“…There are multiple pathologies in AD that contribute to the impairment of neurogenesis. One of the most well‐known and extensively researched pathologies is the accumulation of amyloid‐beta plaques 32 . Amyloid‐beta peptides are produced via the proteolytic processing of transmembrane APP by β‐ and γ‐secretases 33 .…”