TGF-β/Smad signalling has been the subject of extensive research due to its role in the cell cycle and carcinogenesis. Modifications to the TGF-β/Smad signalling pathway have been found to produce disparate effects on neurogenesis. We review the current research on canonical and non-canonical TGF-β/Smad signalling pathways and their functions in neurogenesis. We also examine the observed role of neurogenesis in neuropsychiatric disorders and the relationship between TGF-β/Smad signalling and neurogenesis in response to stressors. Overlapping mechanisms of cell proliferation, neurogenesis, and the development of mood disorders in response to stressors suggest that TGF-β/Smad signalling is an important regulator of stress response and is implicated in the behavioural outcomes of mood disorders.

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 amyloid-beta 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.

A promising direction in the research on Alzheimer’s Disease (AD) is the identification of biomarkers that better inform the disease progression of AD. However, the performance of amyloid-based biomarkers in predicting cognitive performance has been shown to be suboptimal. We hypothesise that neuronal loss could better inform cognitive impairment. We have utilised the 5xFAD transgenic mouse model that displays AD pathology at an early phase, already fully manifested after 6 months. We have evaluated the relationships between cognitive impairment, amyloid deposition, and neuronal loss in the hippocampus in both male and female mice. We observed the onset of disease characterized by the emergence of cognitive impairment in 6-month-old 5xFAD mice coinciding with the emergence of neuronal loss in the subiculum, but not amyloid pathology. We also showed that female mice exhibited significantly increased amyloid deposition in the hippocampus and entorhinal cortex, highlighting sex-related differences in the amyloid pathology of this model. Therefore, parameters based on neuronal loss might more accurately reflect disease onset and progression compared to amyloid-based biomarkers in AD patients. Moreover, sex-related differences should be considered in studies involving 5xFAD mouse models.