scholarly journals Meta-Analysis of the Alzheimer’s Disease Human Brain Transcriptome and Functional Dissection in Mouse Models

Cell Reports ◽  
2020 ◽  
Vol 32 (2) ◽  
pp. 107908 ◽  
Author(s):  
Ying-Wooi Wan ◽  
Rami Al-Ouran ◽  
Carl G. Mangleburg ◽  
Thanneer M. Perumal ◽  
Tom V. Lee ◽  
...  
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Human Brain ◽  
Mouse Models ◽  
Meta Analysis ◽  
Brain Transcriptome

scholarly journals Functional dissection of Alzheimer’s disease brain gene expression signatures in humans and mouse models

2019 ◽  
Author(s):  
Ying-Wooi Wan ◽  
Rami Al-Ouran ◽  
Carl Grant Mangleburg ◽  
Tom V. Lee ◽  
Katherine Allison ◽  
...  
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Human Brain ◽  
Mouse Models ◽  
Neurofibrillary Tangle ◽  
Differentially Expressed Gene ◽  
Experimental Models ◽  
Genetic Manipulations ◽  
Brain Gene Expression ◽  
The Unfolded Protein Response

SUMMARYHuman brain transcriptomes can highlight biological pathways associated with Alzheimer’s disease (AD); however, challenges remain to link expression changes with causal triggers. We have examined 30 AD-associated, gene coexpression modules from human brains for overlap with 251 differentially-expressed gene sets from mouse brain RNA-sequencing experiments, including from models of AD and other neurodegenerative disorders. Human-mouse overlaps highlight responses to amyloid versus neurofibrillary tangle pathology and further reveal age- and sex-dependent expression signatures for AD progression. Human coexpression modules enriched for neuronal and/or microglial genes overlap broadly with signatures from mouse models of AD, Huntington’s disease, Amyotrophic Lateral Sclerosis, and also aging. Several human AD coexpression modules, including those implicated in the unfolded protein response and oxidative phosphorylation, were not activated in AD models, but instead were detected following other, unexpected mouse genetic manipulations. Our results comprise a powerful, cross-species resource and pinpoint experimental models for diverse features of AD pathophysiology from human brain transcriptomes.

scholarly journals Altered synaptic ingestion by human microglia in Alzheimer’s disease

2019 ◽  
Author(s):  
Makis Tzioras ◽  
Michael J.D. Daniels ◽  
Declan King ◽  
Karla Popovic ◽  
Rebecca K. Holloway ◽  
...  
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Human Brain ◽  
Mouse Models ◽  
Disease Risk ◽  
Synaptic Proteins ◽  
Postmortem Brain ◽  
Human Microglia ◽  
Human Postmortem Brain ◽  
Synapse Loss

AbstractSynapse loss correlates strongly with cognitive decline in Alzheimer’s disease, but the mechanisms underpinning this phenomenon remain unclear. Recent evidence from mouse models points to microglial cells as mediators of synapse removal, and human genetic evidence implicates microglia in disease risk. Here we demonstrate that microglia from human postmortem brain contain synaptic proteins and that greater amounts are observed in microglia from Alzheimer’s compared to non-diseased brain tissue. Further, we observe that primary human adult microglia phagocytose synapses isolated from human brain, and that AD brain-derived synapses are phagocytosed more rapidly and abundantly than controls. Together, these data show that synapses in the human AD brain are more prone to ingestion by microglia. Our findings provide evidence from human tissue implicating altered microglial-mediated synaptic uptake in AD pathobiology.One Sentence SummaryAD alters synapse ingestion by microglia

Effect of antihypertensive drugs on cognition and behavioral symptoms of patients with Alzheimer’s disease: A meta-analysis

2020 ◽  
Vol 21 ◽  
Author(s):  
Roja Rahimi ◽  
Shekoufeh Nikfar ◽  
Masoud Sadeghi ◽  
Mohammad Abdollahi ◽  
Reza Heidary Moghaddam ◽  
...  
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Randomized Clinical Trials ◽  
Antihypertensive Drugs ◽  
Meta Analysis ◽  
Behavioral Symptoms ◽  
Cochrane Library ◽  
Mean Differences ◽  
Global Impression Of Change ◽  
State Examination

Background: It has been found that there is a link between hypertension and elevated risk of Alzheimer’s disease (AD). Herein, a meta-analysis based on randomized clinical trials (RCTs) was used to assess the effect of antihypertensive drugs on cognition and behavioral symptoms of AD patients. Method: The three databases – PubMed/Medline, Scopus, and Cochrane Library- were searched up to March 2020. The quality of the studies included in the meta-analysis was evaluated by the Jadad score. Clinical Global Impression of Change (CGIC) included in two studies, Mini-Mental State Examination (MMSE) included in three studies, and Neuropsychiatric Inventory (NPI) in three studies were the main outcomes in this systematic review. Results: Out of 1506 studies retrieved in the databases, 5 RCTs included and analyzed in the meta-analysis. The pooled mean differences of CGIC, MMSE, and NPI in patients with AD receiving antihypertensive drugs compared to placebo was -1.76 with (95% CI = -2.66 to -0.86; P=0.0001), 0.74 (95% CI = 0.20 to 1.28; P= 0.007), and -9.49 (95% CI = -19.76 to 0.79; P = 0.07), respectively. Conclusion: The findings of the present meta-analysis show that antihypertensive drugs may improve cognition and behavioral symptoms of patients with AD. However, more well-designed RCTs with similar drugs are needed to achieve more conclusive results.

Characteristics of Insulin-degrading Enzyme in Alzheimer's Disease: A Meta-Analysis

2018 ◽  
Vol 15 (7) ◽  
pp. 610-617 ◽  
Author(s):  
Huifeng Zhang ◽  
Dan Liu ◽  
Huanhuan Huang ◽  
Yujia Zhao ◽  
Hui Zhou
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Enzyme Activity ◽  
Protein Level ◽  
Senile Plaque ◽  
Meta Analysis ◽  
Cochrane Library ◽  
Insulin Degrading Enzyme ◽  
Degrading Enzyme ◽  
Significant Difference

Background: β-amyloid (Aβ) accumulates abnormally to senile plaque which is the initiator of Alzheimer's disease (AD). As one of the Aβ-degrading enzymes, Insulin-degrading enzyme (IDE) remains controversial for its protein level and activity in Alzheimer's brain. Methods: The electronic databases PubMed, EMBASE, The Cochrane Library, OVID and Sinomed were systemically searched up to Sep. 20th, 2017. And the published case-control or cohort studies were retrieved to perform the meta-analysis. Results: Seven studies for IDE protein level (AD cases = 293; controls = 126), three for mRNA level (AD cases = 138; controls = 81), and three for enzyme activity (AD cases = 123; controls = 75) were pooling together. The IDE protein level was significantly lower in AD cases than in controls (SMD = - 0.47, 95% CI [-0.69, -0.24], p < 0.001), but IDE mRNA and enzyme activity had no significant difference (SMD = 0.02, 95% CI [-0.40, 0.43] and SMD = 0.06, 95% CI [-0.41, 0.53] respectively). Subgroup analyses found that IDE protein level was decreased in both cortex and hippocampus of AD cases (SMD = -0.43, 95% CI [-0.71, -0.16], p = 0.002 and SMD = -0.53, 95% CI [-0.91, -0.15], p = 0.006 respectively). However, IDE mRNA was higher in cortex of AD cases (SMD = 0.71, 95% CI [0.14, 1.29], p = 0.01), not in hippocampus (SMD = -0.26, 95% CI [-0.58, 0.06]). Conclusions: Our results indicate that AD patients may have lower IDE protease level. Further relevant studies are still needed to verify whether IDE is one of the factors affecting Aβ abnormal accumulation and throw new insights for AD detection or therapy.

TREM2 p.H157Y Variant and the Risk of Alzheimer's Disease: A Meta-Analysis Involving 14,510 Subjects

2016 ◽  
Vol 13 (4) ◽  
pp. 318-320 ◽  
Author(s):  
Teng Jiang ◽  
Jian-Kang Hou ◽  
Qing Gao ◽  
Jin-Tai Yu ◽  
Jun-Shan Zhou ◽  
...  
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Meta Analysis
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