Neuroinflammation in Alzheimer’s disease

Abstract

Amyloid-β plaques and neurofibrillary tangles are the main neuropathological hallmarks in Alzheimer’s disease (AD), the most common cause of dementia in the elderly. However, it has become increasingly apparent that neuroinflammation plays a significant role in the pathophysiology of AD. This review summarizes the current status of neuroinflammation research related to AD, focusing on the connections between neuroinflammation and some inflammation factors in AD. Among these connections, we discuss the dysfunctional blood–brain barrier and alterations in the functional responses of microglia and astrocytes in this process. In addition, we summarize and discuss the role of intracellular signaling pathways involved in inflammatory responses in astrocytes and microglia, including the mitogen-activated protein kinase pathways, nuclear factor-kappa B cascade, and peroxisome proliferator–activated receptor-gamma transcription factors. Finally, the dysregulation of the control and release of pro- and anti-inflammatory cytokines and classic AD pathology (amyloid plaques and neurofibrillary tangles) in AD is also reviewed.

Humulus japonicus inhibits the progression of Alzheimer's disease in a APP/PS1 transgenic mouse model

“…Furthermore, the anti-inflammatory activities of HJ were revealed in HJ-treated Tg-APP/PS1 mice; the activation of microglia and astrocytes, and the mRNA expression of TNF-α and IL-6, the major cytokines in the process of AD pathogenesis, was markedly decreased in the cortex tissues of HJ-treated Tg-APP/PS1 mice. Chronic neuroinflammation induced by pro-inflammatory cytokines released from activated microglia and astrocytes has been recognized as one of the major mechanisms of AD pathophysiology (3). Aβ plaques and tangles in the brains of patients with AD stimulate a chronic inflammatory reaction to clear this debris (35–37).…”

“…Amyloid β (Aβ) aggregation and accumulation in the brain is considered a causative factor in the pathogenesis of AD, while the progression of AD is considered to be multifactorial, and involves an increase in oxidative stress and inflammation (1–3). The increased accumulation of cellular reactive oxygen species (ROS) and oxidative damage to lipids, nucleic acids and proteins, as well as the activation of inflammatory responses are considered to play major roles in the process of age-related neurodegeneration and cognitive decline (3–7). …”

“…Reactive glial cells, microglia and astrocytes produce multiple inflammatory factors, including cytokines, chemokines, ROS and cyclooxygenase-2 (COX-2). Elevated levels of these factors have been discovered in AD and are among the major mechanisms of AD neuropathology (3,8). Anti-inflammatory drugs, such as non-steroidal anti-inflammatory drugs, peroxisome proliferator-activated receptor-γ agonists, minocycline, and tumor necrosis factor-α (TNF-α) inhibitors attenuate microglial activation, amyloid deposition and tau hyperphosphorylation in animal models of AD (9–14).…”

Effect of stent-assisted angioplasty on cognitive status and serum levels of amyloid beta in patients with intracranial and/or extracranial artery stenosis

“…Aβ fragments are hydrophobic peptides consisting of 40–42 residues derived from the sequential cleavage of APP by proteinases and beta (β)- and gamma (γ)-secretases. An imbalance between production and clearance of Aβ fragments may cause abnormal accumulation of these peptides inside the brain and the subsequent development of AD 14,15…”

Stem Cell Therapy: A Prospective Treatment for Alzheimer's Disease

“…In recent findings, the importance of glial cells and intercellular binding proteins in shaping the external environments of neurons have been suggested. The decline of microglia, astrocytes and oligodendrocytes that support the neuronal networks in the CNS through immune, nutritional and homeostatic mechanisms are correlated with the neuroinflammatory biochemistry of AD 4142. Additionally, the deterioration of central binding proteins between neurons such as Slitrk and LAR-RPTP contributes to the widespread neuronal loss 434445.…”