Imagine Alzheimer’s disease as a complex puzzle. Researchers are tirelessly working to decode the intricate pathways involved in its progression and understand the underlying dysfunctions. One key puzzle piece is the JAK2/STAT3 pathway, which shows elevated protein levels in AD models. But it’s not just neurons that play a role – astrocytes, a type of glial cell, have their part to play too. Another missing link is the failure in the NGF metabolic pathway, essential for the survival of cholinergic neurons. Experiments have shown promise in using exogenous mNGF to restore these neurons. Meanwhile, the FGF7/FGFR2/PI3K/Akt signaling pathway mediated by microRNA-107 has also emerged as a player in AD pathogenesis. Vascular dysfunction is another important factor, with risk factors like apolipoprotein E4 polymorphism contributing to cognitive decline. And finally, metabolomics – analyzing neurotransmitters and nutrients – has opened up new possibilities for diagnosing and predicting neurodegenerative diseases. To delve deeper into these fascinating findings and get a well-rounded perspective on Alzheimer’s, don’t miss out on exploring the underlying research!

Alzheimer’s disease (AD) is an irreversible brain disorder associated with slow, progressive loss of brain functions mostly in older people. The disease processes start years before the symptoms are manifested at which point most therapies may not be as effective. In the hippocampus, the key proteins involved in the JAK2/STAT3 signaling pathway, such as p-JAK2-Tyr1007 and p-STAT3-Tyr705 were found to be elevated in various models of AD. In addition to neurons, glial cells such as astrocytes also play a crucial role in the progression of AD. Without having a significant effect on tau and amyloid pathologies, the JAK2/STAT3 pathway in reactive astrocytes exhibits a behavioral impact in the experimental models of AD. Cholinergic atrophy in AD has been traced to a trophic failure in the NGF metabolic pathway, which is essential for the survival and maintenance of basal forebrain cholinergic neurons (BFCN). In AD, there is an alteration in the conversion of the proNGF to mature NGF (mNGF), in addition to an increase in degradation of the biologically active mNGF. Thus, the application of exogenous mNGF in experimental studies was shown to improve the recovery of atrophic BFCN. Furthermore, it is now coming to light that the FGF7/FGFR2/PI3K/Akt signaling pathway mediated by microRNA-107 is also involved in AD pathogenesis. Vascular dysfunction has long been associated with cognitive decline and increased risk of AD. Vascular risk factors are associated with higher tau and cerebral beta-amyloid (Aβ) burden, while synergistically acting with Aβ to induce cognitive decline. The apolipoprotein E4 polymorphism is not just one of the vascular risk factors, but also the most prevalent genetic risk factor of AD. More recently, the research focus on AD shifted toward metabolisms of various neurotransmitters, major and minor nutrients, thus giving rise to metabolomics, the most important “omics” tool for the diagnosis and prognosis of neurodegenerative diseases based on an individual’s metabolome. This review will therefore proffer a better understanding of novel signaling pathways associated with neural and glial mechanisms involved in AD, elaborate potential links between vascular dysfunction and AD, and recent developments in “omics”-based biomarkers in AD.

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