Neuroinflammation in mouse models of Alzheimer's disease

Abstract

Alzheimer's disease (AD) is the most common type of neurocognitive disorder. Although both amyloid β peptide deposition and neurofibrillary tangle formation in the AD brain have been established as pathological hallmarks of the disease, many other factors contribute in a complex manner to the pathogenesis of AD before clinical symptoms of the disease become apparent. Longitudinal pathophysiological processes cause patients’ brains to exist in a state of chronic neuroinflammation, with glial cells acting as key regulators of the neuroinflammatory state. However, the detailed molecular and cellular mechanisms of glial function underlying AD pathogenesis remain elusive. Furthermore, recent studies have shown that peripheral inflammatory conditions affect glial cells in the brain through a process of neuroimmune communication. Such disease complexities make it difficult for the pathogenesis of AD to be understood, and impede the development of effective therapeutic strategies to combat the disease. Relevant AD animal models are thus likely to serve as a key resource to overcome many of these issues. Furthermore, as the pathogenesis of AD might be linked to conditions both within the brain as well as peripherally, it might become necessary for AD to be studied as a whole‐body disorder. The present review aimed to summarize insights regarding current AD research, and share perspectives for understanding glial function in the context of the pathogenesis of AD.

Cerebrospinal fluid sTREM2 in Alzheimer’s disease: comparisons between clinical presentation and AT classification

“…Interestingly in the absence of TREM2, with elimination of this checkpoint function, neuritic dystrophy and phospho-tau immunoreactivity increased around senile plaques in transgenic mice seeded with human tau-aggregates 45 . Although studies with genetically manipulated models like here a knock-out model 45 and sporadic AD patients can create vastly different outcomes 46,47 the findings both link the same pathogenic processes; tauopathy with microgliosis/TREM2. Although the results seem opposite, they may not be as biological processes create responses by functioning in networks.…”

Positive selection and gene duplications in tumour suppressor genes reveal clues about how cetaceans resist cancer

“…In cetaceans, we report multiple copies of genes that has been recognized as a genetic risk factors in human Alzheimer's. Some of those genes are EPHA1, that is a positive regulator of angiogenesis, and metastases 69 ; the ACHE gene, that encodes for the enzyme acetylcholinesterase, which is a catabolic enzyme for the neurotransmitter acetylcholine that is involved in the nervous system development pathways 70 and the BIN1 gene, that is a neuroinflammation related gene 71 . Particularly, for the BIN1 gene we found eleven copies in the beluga, eight in the river dolphin and four in the killer whale.…”

Innate immune adaptor TRIF deficiency accelerates disease progression of ALS mice with accumulation of aberrantly activated astrocytes

“…Then, they reviewed many aspects of glial cell involvement in AD, and extended their view on the neuroinflammation and interaction between the brain and whole-body macroenvironment. 6 Trias et al reviewed the role of astrocytes in ALS, an adult neurodegenerative disease characterized by selective death of motor neurons. 7 By the use of selective gene ablation of ALS-causing mutant genes from an ALS mouse model, they showed the active roles of astrocytes in disease progression.…”