scholarly journals Microglia, TREM2, and Therapeutic Methods of Alzheimer’s Disease

2021 ◽  
Author(s):  
Siwei Xu ◽  
Yaya Ji ◽  
Tianle Sha ◽  
Haoming Li
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Dynamic Change ◽  
Amyloid Β ◽  
Neuronal Loss ◽  
Pathological Process ◽  
Amyloid Β Protein ◽  
Transmembrane Glycoprotein ◽  
Β Protein ◽  
The Central Nervous System

Alzheimer’s disease (AD) is one of the most common causes of dementia all around the world. It is characterized by the deposition of amyloid-β protein (Aβ) and the formation of neurofibrillary tangles (NFTs), which contribute to neuronal loss and cognitive decline. Microglia, as innate immune cells in brain, plays dual roles in the pathological process of AD. Expression in different subtypes of microglia is diverse in AD genes. Triggering receptor expressed on myeloid cells 2 (TREM2) is a transmembrane glycoprotein mainly expressed on microglia in the central nervous system (CNS). Soluble TREM2 (sTREM2), a proteolytic product of TREM2, which is abundant in the cerebrospinal fluid, shows a dynamic change in different stages and ameliorates the pathological process of AD. The interplay between the different subtypes of apolipoprotein and TREM2 is closely related to the mechanism of AD and serves as important regulatory sites. Moreover, several therapeutic strategies targeting TREM2 have shown positive outcomes during clinical trials and some novel therapies at different points are in progress. In this review, we mainly talk about the interrelationships among microglia, TREM2, and AD, and hope to give an overview of the strategies of AD.

Phosphorylation and Glycosylation of Amyloid-β Protein Precursor: The Relationship to Trafficking and Cleavage in Alzheimer’s Disease

2021 ◽  
pp. 1-21
Author(s):  
Xi-Jun Song ◽  
He-Yan Zhou ◽  
Yu-Ying Sun ◽  
Han-Chang Huang
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Neurodegenerative Disorder ◽  
Senile Plaques ◽  
Amyloid Β ◽  
Amyloid Β Protein ◽  
Protein Precursor ◽  
Β Protein ◽  
Cleavage Enzyme ◽  
The Central Nervous System

Alzheimer’s disease (AD) is a neurodegenerative disorder in the central nervous system, and this disease is characterized by extracellular senile plaques and intracellular neurofibrillary tangles. Amyloid-β (Aβ) peptide is the main constituent of senile plaques, and this peptide is derived from the amyloid-β protein precursor (AβPP) through the successive cleaving by β-site AβPP-cleavage enzyme 1 (BACE1) and γ-secretase. AβPP undergoes the progress of post-translational modifications, such as phosphorylation and glycosylation, which might affect the trafficking and the cleavage of AβPP. In the recent years, about 10 phosphorylation sites of AβPP were identified, and they play complex roles in glycosylation modification and cleavage of AβPP. In this article, we introduced the transport and the cleavage pathways of AβPP, then summarized the phosphorylation and glycosylation sites of AβPP, and further discussed the links and relationship between phosphorylation and glycosylation on the pathways of AβPP trafficking and cleavage in order to provide theoretical basis for AD research.

Normal Production of the Amyloid β-Protein and the Pathogenesis of Alzheimer’s Disease

1995 ◽  
pp. 95-97
Author(s):  
Dennis J. Selkoe ◽  
Christian Haass ◽  
Michael Schlossmacher ◽  
Albert Hung ◽  
Martin Citron ◽  
...  
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Amyloid Β ◽  
Amyloid Β Protein ◽  
Β Protein ◽  
Normal Production

scholarly journals The Alzheimer's Disease-Associated Amyloid β-Protein Is an Antimicrobial Peptide

PLoS ONE ◽  
2010 ◽  
Vol 5 (3) ◽  
pp. e9505 ◽  
Author(s):  
Stephanie J. Soscia ◽  
James E. Kirby ◽  
Kevin J. Washicosky ◽  
Stephanie M. Tucker ◽  
Martin Ingelsson ◽  
...  
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Antimicrobial Peptide ◽  
Amyloid Β ◽  
Amyloid Β Protein ◽  
Β Protein

Mutant presenilins of Alzheimer's disease increase production of 42-residue amyloid β-protein in both transfected cells and transgenic mice

1997 ◽  
Vol 3 (1) ◽  
pp. 67-72 ◽  
Author(s):  
Martin Citron ◽  
David Westaway ◽  
Weiming Xia ◽  
George Carlson ◽  
Thekla Diehl ◽  
...  
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Transgenic Mice ◽  
Amyloid Β ◽  
Amyloid Β Protein ◽  
Transfected Cells ◽  
Β Protein

scholarly journals Amyloid-beta uptake by blood monocytes is reduced with ageing and Alzheimer’s disease

2020 ◽  
Vol 10 (1) ◽  
Author(s):  
Si-Han Chen ◽  
Ding-Yuan Tian ◽  
Ying-Ying Shen ◽  
Yuan Cheng ◽  
Dong-Yu Fan ◽  
...  
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Amyloid Β ◽  
Blood Levels ◽  
Amyloid Β Protein ◽  
Blood Monocytes ◽  
Cognitively Normal ◽  
Β Protein ◽  
Toll Like Receptor 2 ◽  
Age And Sex

AbstractDeficits in the clearance of amyloid β-protein (Aβ) play a pivotal role in the pathogenesis of sporadic Alzheimer’s disease (AD). The roles of blood monocytes in the development of AD remain unclear. In this study, we sought to investigate the alterations in the Aβ phagocytosis function of peripheral monocytes during ageing and in AD patients. A total of 104 cognitively normal participants aged 22–89 years, 24 AD patients, 25 age- and sex-matched cognitively normal (CN) subjects, 15 Parkinson’s disease patients (PD), and 15 age- and sex-matched CN subjects were recruited. The Aβ uptake by blood monocytes was measured and its alteration during ageing and in AD patients were investigated. Aβ1-42 uptake by monocytes decreased during ageing and further decreased in AD but not in PD patients. Aβ1-42 uptake by monocytes was associated with Aβ1-42 levels in the blood. Among the Aβ uptake-related receptors and enzymes, the expression of Toll-like receptor 2 (TLR2) was reduced in monocytes from AD patients. Our findings suggest that monocytes regulate the blood levels of Aβ and might be involved in the development of AD. The recovery of the Aβ uptake function by blood monocytes represents a potential therapeutic strategy for AD.

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