scholarly journals Impaired Innate Immunity Mechanisms in the Brain of Alzheimer’s Disease

2020 ◽  
Vol 21 (3) ◽  
pp. 1126 ◽  
Author(s):  
Martina Romagnoli ◽  
Elisa Porcellini ◽  
Ilaria Carbone ◽  
Robert Veerhuis ◽  
Federico Licastro
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Expression Profiles ◽  
Temporal Cortex ◽  
Gene Expression Profiles ◽  
Mrna Levels ◽  
Virus Infections ◽  
Apoe Ε4 ◽  
Age Related ◽  
Persistent Virus

Among environmental factors likely associated with Alzheimer’s disease (AD), persistent virus infections, and age-related progressive decline of immune competence might play a pivotal role. However, AD antimicrobial brain immune responses are poorly investigated. The present study focused on genes involved in antimicrobial defenses, especially against virus infections, in the AD brain. In particular, mRNA levels of IRF7, MED23, IL28B, and IFN-α genes were analyzed in hippocampus and temporal cortex brain samples from AD and non-demented controls. All subjects were also genotyped for APOE ε, IRF7, MED23, and IL28B gene polymorphisms. Most AD patients showed decreased mRNA levels of all investigated genes in the hippocampus and temporal cortex. However, a small group of AD patients showed increased hippocampal mRNA expression of MED23, IL28B, and IFN-α. mRNA levels of MED23, IL28B, IFN-α from the hippocampus and those of MED23 from the temporal cortex were further decreased in APOE ε4 allele AD carriers. Moreover, rs6598008 polymorphism of IRF7 was significantly associated with decreased hippocampal expression of IRF7, MED23, IL28B, and IFN-α. These findings suggest that AD brains show impaired innate antimicrobial gene expression profiles, and individual genetic makeup, such as positivity for the APOE ε4 and IRF7 A alleles, might affect brain immune efficiency.

Gene expression profiles of metabolic enzyme transcripts in Alzheimer's disease

2007 ◽  
Vol 1127 ◽  
pp. 127-135 ◽  
Author(s):  
Wendy M. Brooks ◽  
Patrick J. Lynch ◽  
Catherine C. Ingle ◽  
Alexander Hatton ◽  
Piers C. Emson ◽  
...  
Keyword(s):  
Gene Expression ◽  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Expression Profiles ◽  
Gene Expression Profiles ◽  
Metabolic Enzyme

Gene Expression Profiles of Entorhinal Cortex in Alzheimer’s Disease

2014 ◽  
Vol 29 (6) ◽  
pp. 526-532 ◽  
Author(s):  
Bingqian Ding ◽  
Yan Xi ◽  
Ming Gao ◽  
Zhenjiang Li ◽  
Chenyang Xu ◽  
...  
Keyword(s):  
Gene Expression ◽  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Entorhinal Cortex ◽  
Expression Profiles ◽  
Gene Expression Profiles

scholarly journals A Chinese Herbal Formula, Gengnianchun, Amelioratesβ-Amyloid Peptide Toxicity in aCaenorhabditis elegansModel of Alzheimer’s Disease

2017 ◽  
Vol 2017 ◽  
pp. 1-10 ◽  
Author(s):  
Fanhui Meng ◽  
Jun Li ◽  
Yanqiu Rao ◽  
Wenjun Wang ◽  
Yan Fu
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Neurodegenerative Disorder ◽  
Amyloid Peptide ◽  
Mrna Levels ◽  
Pheochromocytoma Cells ◽  
C Elegans ◽  
Chinese Herbal ◽  
Chinese Medicine Formula ◽  
Age Related

Alzheimer’s disease (AD) is an age-related neurodegenerative disorder, and the few drugs that are currently available only treat the symptoms. Traditional medicine or phytotherapy has been shown to protect against AD. In our previous studies, Gengnianchun (GNC), a traditional Chinese medicine formula with a prolongevity effect, protected against Aβ-induced cytotoxicity in pheochromocytoma cells (PC-12 cells) and hippocampal cells. Here, we investigated the effects and possible mechanisms by which GNC protected against Aβtoxicity using transgenicCaenorhabditis elegansCL4176. Our results showed that GNC effectively delayed the Aβtoxicity-triggered body paralysis of CL4176 worms. GNC decreased Aβby reducing AβmRNA levels. Moreover, GNC significantly reduced reactive oxygen species in the AD model worms compared with the controls. In addition, GNC upregulated the daf-16, sod-3, hsp-16.2 genes, and enhanced DAF-16 translocation from the cytoplasm to the nuclei under oxidative stress conditions. GNC treatment ofC. elegansstrains lacking DAF-16 did not affect the paralysis phenotype. Taken together, these findings suggest that GNC could protect against Aβ-induced toxicity via the DAF-16 pathway inC. elegans. Further studies are required to analyze its effectiveness in more complex animals.

scholarly journals Transcriptional dysregulation study reveals a core network involving the genesis for Alzheimer’s disease

2017 ◽  
Author(s):  
Guofeng Meng ◽  
Hongkang Mei
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Expression Profiles ◽  
Gene Expression Profiles ◽  
Synaptic Function ◽  
Core Network ◽  
Disease Etiology ◽  
Transcriptional Dysregulation ◽  
Disease States ◽  
Human And Mouse

AbstractBackgroundThe pathogenesis of Alzheimer’s disease is associated with dysregulation at different levels from transcriptome to cellular functioning. Such complexity necessitates investigations of disease etiology to be carried out considering multiple aspects of the disease and the use of independent strategies. The established works more emphasized on the structural organization of gene regulatory network while neglecting the internal regulation changes.MethodsApplying a strategy different from popularly used co-expression network analysis, this study investigated the transcriptional dysregulations during the transition from normal to disease states.Results97 genes were predicted as dysregulated genes, which were also associated with clinical outcomes of Alzheimer’s disease. Both the co-expression and differential co-expression analysis suggested these genes to be interconnected as a core network and that their regulations were strengthened during the transition to disease states. Functional studies suggested the dysregulated genes to be associated with aging and synaptic function. Further, we checked the evolutionary conservation of the gene co-expression and found that human and mouse brain might have divergent transcriptional co-regulation even when they had conserved gene expression profiles.ConclusionOverall, our study reveals a profile of transcriptional dysregulation in the genesis of Alzheimer’s disease by forming a core network with altered regulation; the core network is associated with Alzheimer’s diseases by affecting the aging and synaptic functions related genes; the gene regulation in brain may not be conservative between human and mouse.

scholarly journals Effect of APOE ε4 genotype on amyloid-β and tau accumulation in Alzheimer’s disease

2020 ◽  
Author(s):  
Min Seok Baek ◽  
Hanna Cho ◽  
Hye Sun Lee ◽  
Jae Hoon Lee ◽  
Young Hoon Ryu ◽  
...  
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Accumulation Rate ◽  
Temporal Cortex ◽  
Amyloid Β ◽  
Standardized Uptake Value ◽  
Linear Mixed Effect Model ◽  
Mixed Effect ◽  
Apoe Ε4 ◽  
Pet Scans

Abstract Background: To assess effects of apolipoprotein E (ApoE) ε4 genotype on Aβ and tau burden and their longitudinal changes in Alzheimer’s disease (AD) spectrum.Methods: Among 272 individuals who underwent PET scans (18F-florbetaben for Aβ and 18F-flortaucipir for tau) and ApoE genotyping, 187 individuals completed 2-year follow-up PET scans. After correcting for partial-volume effect, we compared the standardized uptake value ratio (SUVR) for Aβ and tau burden between the ε4+ and ε4- groups. By using a linear mixed-effect model, we measured changes in SUVR in the ApoE ε4+ and ε4- groups.Results: The ε4+ group showed greater baseline Aβ burden in the diffuse cortical regions and greater tau burden in the lateral, and medial temporal, cingulate, and insula cortices. Tau accumulation rate was higher in the parietal, occipital, lateral, and medial temporal cortices in the ε4+ group. In Aβ+ individuals, baseline tau burden was greater in the medial temporal cortex, while Aβ burden was conversely greater in the ε4- group. Tau accumulation rate was higher in the ε4+ group in a small region in the lateral temporal cortex. The effect of ApoE ε4 on enhanced tau accumulation persisted even after adjusting for the global cortical Aβ burden.Conclusions: Progressive tau accumulation may be more prominent in ε4 carriers, particularly in the medial and lateral temporal cortices. ApoE ε4 allele has differential effects on Aβ burden depending on the existing amyloidosis and enhances vulnerability to progressive tau accumulation in the AD spectrum independent of Aβ.

scholarly journals Supervised pathway analysis of blood gene expression profiles in Alzheimer's disease

2019 ◽  
Vol 84 ◽  
pp. 98-108 ◽  
Author(s):  
Elaheh Moradi ◽  
Mikael Marttinen ◽  
Tomi Häkkinen ◽  
Mikko Hiltunen ◽  
Matti Nykter
Keyword(s):  
Gene Expression ◽  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Pathway Analysis ◽  
Expression Profiles ◽  
Gene Expression Profiles ◽  
Blood Gene Expression
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