scholarly journals Therapeutic Potential of Neu1 in Alzheimer’s Disease Via the Immune System

2021 ◽  
Vol 36 ◽  
pp. 153331752199614
Author(s):  
Aiza Khan ◽  
Sumit Das ◽  
Consolato Sergi
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Immune System ◽  
Therapeutic Potential ◽  
Amyloid Plaques ◽  
Beta Amyloid ◽  
Underlying Mechanism ◽  
Amyloid Deposits ◽  
Potential Therapeutic Role

Alzheimer’s Disease (AD) is pathologically characterized by the accumulation of soluble oligomers causing extracellular beta-amyloid deposits in form of neuritic plaques and tau-containing intraneuronal neurofibrillary tangles in brain. One proposed mechanism explaining the formation of these proteins is impaired phagocytosis by microglia/macrophages resulting in defective clearance of soluble oligomers of beta-amyloid stimulating aggregation of amyloid plaques subsequently causing AD. However, research indicates that activating macrophages in M2 state may reduce toxic oligomers. NEU1 mutation is associated with a rare disease, sialidosis. NEU1 deficiency may also cause AD-like amyloidogenic process. Amyloid plaques have successfully been reduced using NEU1.Thus, NEU1 is suggested to have therapeutic potential for AD, with lysosomal exocytosis being suggested as underlying mechanism. Studies however demonstrate that NEU1 may activate macrophages in M2 state, which as noted earlier, is crucial to reducing toxic oligomers. In this review, authors discuss the potential therapeutic role of NEU1 in AD via immune system.

scholarly journals C99 selectively accumulates in vulnerable neurons in Alzheimer’s disease

2019 ◽  
Author(s):  
Maria V. Pulina ◽  
Maya Hopkins ◽  
Vahram Haroutunian ◽  
Paul Greengard ◽  
Victor Bustos
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Cognitive Impairment ◽  
Amyloid Precursor Protein ◽  
Amyloid Plaques ◽  
Beta Amyloid ◽  
Sensitive Assay ◽  
Brain Areas ◽  
Amyloid Deposits ◽  
The Brain

ABSTRACTIntroductionThe levels and distribution of amyloid deposits in the brain does not correlate well with Alzheimer’s disease (AD) progression. Therefore, it is likely that Amyloid-precursor-protein proteolytic fragments other than beta-amyloid contribute to the onset of AD.MethodsWe developed a sensitive assay adapted to the detection of C99, the direct precursor of beta-amyloid. Three postmortem groups were studied: control with normal and stable cognition; subjects with moderate AD, and individuals with severe AD. The amount of C99 and beta-amyloid was quantified and correlated with the severity of AD.ResultsC99 accumulates in vulnerable neurons, and its levels correlate with the degree of cognitive impairment in patients suffering from AD. In contrast, beta-amyloid levels are increased in both vulnerable and resistant brain areas.DiscussionThese results raise the possibility that C99, rather than beta-amyloid plaques, is responsible for the death of nerve cells in Alzheimer’s disease.

scholarly journals TREM2 deficiency eliminates TREM2+ inflammatory macrophages and ameliorates pathology in Alzheimer’s disease mouse models

2015 ◽  
Vol 212 (3) ◽  
pp. 287-295 ◽  
Author(s):  
Taylor R. Jay ◽  
Crystal M. Miller ◽  
Paul J. Cheng ◽  
Leah C. Graham ◽  
Shane Bemiller ◽  
...  
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
High Risk ◽  
Mouse Models ◽  
Myeloid Cells ◽  
Cell Types ◽  
Targeted Therapeutics ◽  
Amyloid Deposits ◽  
Inflammatory Macrophages

Variants in triggering receptor expressed on myeloid cells 2 (TREM2) confer high risk for Alzheimer’s disease (AD) and other neurodegenerative diseases. However, the cell types and mechanisms underlying TREM2’s involvement in neurodegeneration remain to be established. Here, we report that TREM2 is up-regulated on myeloid cells surrounding amyloid deposits in AD mouse models and human AD tissue. TREM2 was detected on CD45hiLy6C+ myeloid cells, but not on P2RY12+ parenchymal microglia. In AD mice deficient for TREM2, the CD45hiLy6C+ macrophages are virtually eliminated, resulting in reduced inflammation and ameliorated amyloid and tau pathologies. These data suggest a functionally important role for TREM2+ macrophages in AD pathogenesis and an unexpected, detrimental role of TREM2 in AD pathology. These findings have direct implications for future development of TREM2-targeted therapeutics.

scholarly journals Genome research in pre-dementia stages of Alzheimer's disease

2016 ◽  
Vol 18 ◽  
Author(s):  
Sonia Moreno-Grau ◽  
Agustín Ruiz
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Late Onset ◽  
Subjective Cognitive Decline ◽  
Genetic Profile ◽  
Amyloid Deposits ◽  
Dementia Risk ◽  
Meta Analyses ◽  
Brain Insults

Genetic characterization of individuals at risk of Alzheimer's disease (AD), i.e. people having amyloid deposits in the brain without symptoms, people suffering from subjective cognitive decline (SCD) or mild cognitive impairment (MCI), has spurred the interests of researchers. However, their pre-dementia genetic profile remains mostly unexplored. In this study, we reviewed the loci related to phenotypes of AD, MCI and SCD from literature and performed the first meta-analyses evaluating the role of apolipoprotein E (APOE) in the risk of conversion from a healthy status to MCI and SCD. For AD dementia risk, an increased number of loci have been identified; to date, 28 genes have been associated with Late Onset AD. In MCI syndrome,APOEis confirmed as a pheno-conversion factor leading from MCI to AD, and clusterin is a promising candidate. Additionally, our meta-analyses revealedAPOEas genetic risk factor to convert from a healthy status to MCI [OR = 1.849 (1.587–2.153);P = 2.80  × 10−15] and to a lesser extent from healthy status to SCD [OR = 1.151 (1.015–1.304);P = 0.028]. Thus, we believe that genetic studies in longitudinal SCD and MCI series may provide new therapeutic targets and improve the existing knowledge of AD. This type of studies must be completed on healthy subjects to better understand the natural disease resistance to brain insults and neurodegeneration.

Selenomethionine reduces the deposition of beta-amyloid plaques by modulating β-secretase and enhancing selenoenzymatic activity in a mouse model of Alzheimer's disease

Metallomics ◽  
2016 ◽  
Vol 8 (8) ◽  
pp. 782-789 ◽  
Author(s):  
Zhong-Hao Zhang ◽  
Chen Chen ◽  
Qiu-Yan Wu ◽  
Rui Zheng ◽  
Qiong Liu ◽  
...  
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Mouse Model ◽  
Amyloid Plaques ◽  
Beta Amyloid ◽  
Model Of Alzheimer’S Disease ◽  
Aβ Production

Effects on Aβ production and the probable connection among selenoenzymes, GSK3β and Aβ pathology by selenomethionine treatment in AD mice.

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