Pathogenic microbes, the microbiome, and Alzheimer’s disease (AD)

doi:10.3389/fnagi.2014.00127

Cited by 105 publications

(103 citation statements)

References 59 publications

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“…1b, c) [15, 22, 26, 27]. For example, pooling of AD samples in one group and age-matched controls in another using the same anatomical region matched for age, gender, and PMI, it was recently possible to show (i) significant reductions in AD of the triggering receptor expressed in myeloid/microglial cells (TREM2) sensor-receptor, a microglial-resident glycoprotein important in the clearance of amyloid peptides from the brain’s extracellular space [28] and (ii) statistically significant individual differences in abundance and complexity of a subfamily of pathology-associated and AD-relevant miRNAs between Caucasian and African-American populations [22, 41].…”

Section: Discussionmentioning

confidence: 99%

“…Over 99 % of the microbiota in the GI tract are anaerobic bacteria with fungi, protozoa, archaebacteria, and other microorganisms making up the remainder; remarkably, the number of microbial cells in the human microbiome outnumber human host cells by about 100 to 1 [14, 15]. At the point of death, the human microbiome rapidly transforms into the thanatomicrobiome ( thanatos -, Greek, death) and begins to play an important role in the decomposition of tissues.…”

Section: The Thanatomicrobiome and Agonal Processesmentioning

confidence: 99%

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Analysis of RNA from Alzheimer’s Disease Post-mortem Brain Tissues

et al. 2015

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Alzheimer’s disease (AD) is a uniquely human, age-related central nervous system (CNS) disorder for which there is no adequate experimental model. While well over 100 transgenic murine models of AD (TgAD) have been developed that recapitulate many of the neuropathological features of AD, key pathological features of AD such as progressive neuronal atrophy, neuron cell loss, and neurofibrillary tangle (NFT) formation have not been observed in any TgAD model to date. To more completely analyze and understand the neuropathology, altered neuro-inflammatory and innate-immune signaling pathways, and the complex molecular-genetics and epigenetics of AD, it is therefore necessary to rigorously examine short post-mortem interval (PMI) human brain tissues to gain a deeper and more thorough insight into the neuropathological mechanisms that characterize the AD process. This perspective-methods paper will highlight some important recent findings on the utilization of short PMI tissues in sporadic (idiopathic; of unknown origin) AD research with focus on the extraction and quantification of RNA, and in particular microRNA (miRNA) and messenger RNA (mRNA) and analytical strategies, drawing on the authors’ combined 125 years of laboratory experience into this investigative research area. We sincerely hope that new investigators in the field of “gene expression analysis in neurological disease” will benefit from the observations presented here and incorporate these recent findings and observations into their future experimental planning and design.

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Section: Discussionmentioning

confidence: 99%

Section: The Thanatomicrobiome and Agonal Processesmentioning

confidence: 99%

Analysis of RNA from Alzheimer’s Disease Post-mortem Brain Tissues

et al. 2015

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“…Moreover, they are found to involve in the microbiota-gut-brain axis bidirectionally connecting neural [26], immune [27], endocrine [28] and metabolic pathways [29,30]. Recent studies suggest that the gut microbiota play a critical role in neurodegenerative diseases including AD or various types of dementia [31,32]. Pilot studies reported that glutamate metabolized by gut microbiota can be linked to obesity [33], seizure [34], autism [35] and cognition [36,37].…”

Section: Introductionmentioning

confidence: 99%

d-glutamate and Gut Microbiota in Alzheimer’s Disease

Chang

Lin

Lane

2020

IJMS

131

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Background: An increasing number of studies have shown that the brain–gut–microbiota axis may significantly contribute to Alzheimer’s disease (AD) pathogenesis. Moreover, impaired memory and learning involve the dysfunction neurotransmission of glutamate, the agonist of the N-methyl-d-aspartate receptor and a major excitatory neurotransmitter in the brain. This systematic review aimed to summarize the current cutting-edge research on the gut microbiota and glutamate alterations associated with dementia. Methods: PubMed, the Cochrane Collaboration Central Register of Controlled Clinical Trials, and Cochrane Systematic Reviews were reviewed for all studies on glutamate and gut microbiota in dementia published up until Feb 2020. Results: Several pilot studies have reported alterations of gut microbiota and metabolites in AD patients and other forms of dementia. Gut microbiota including Bacteroides vulgatus and Campylobacter jejuni affect glutamate metabolism and decrease the glutamate metabolite 2-keto-glutaramic acid. Meanwhile, gut bacteria with glutamate racemase including Corynebacterium glutamicum, Brevibacterium lactofermentum, and Brevibacterium avium can convert l-glutamate to d-glutamate. N-methyl-d-aspartate glutamate receptor (NMDAR)-enhancing agents have been found to potentially improve cognition in AD or Parkinson’s disease patients. These findings suggest that d-glutamate (d-form glutamate) metabolized by the gut bacteria may influence the glutamate NMDAR and cognitive function in dementia patients. Conclusions: Gut microbiota and glutamate are potential novel interventions to be developed for dementia. Exploring comprehensive cognitive functions in animal and human trials with glutamate-related NMDAR enhancers are warranted to examine d-glutamate signaling efficacy in gut microbiota in patients with AD and other neurodegenerative dementias.

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“…Together these suggest a remarkably extensive similarity of miRNA actions to the pathogenic functions imparted by plant viroids. Hence, nature appears to have adopted several common biochemical and genetic strategies conserved over many hundreds of millions of years of eukaryotic evolution involving this particular type of post-transcriptional regulatory control of gene expression [30][31][32][33][34][35][36][37].…”

Section: Mirna Stability and Structural Conservationmentioning

confidence: 99%

microRNA (miRNA)-Mediated Pathogenetic Signaling in Alzheimer’s Disease (AD)

Hill

Lukiw

2015

Neurochem Res

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Alzheimer's disease (AD) is an expanding health and socioeconomic concern in industrialized societies, and the leading cause of intellectual impairment in our aging population. The cause of AD remains unknown, and there are currently no effective treatments to stop or reverse the progression of this uniquely human and age-related neurological disorder. Elucidation of the AD mechanism and factors that contribute to the initiation, progression, and spreading of this chronic and fatal neurodegeneration will ultimately result in improved and effective diagnostics and therapeutic strategies.microRNAs (miRNAs) comprise a relatively recently discovered category of 20-24 nucleotide non-coding RNAs that function post-transcriptionally in shaping the transcriptome of the cell, and in doing so, contribute to the molecular-genetics and phenotype of human CNS health and disease. To date about 2550 unique mature human miRNAs have been characterized, however only highly selected miRNA populations appear to be enriched in different anatomical compartments within the CNS.This general commentary for the 'Special Issue: 40th Year of Neurochemical Research' will bring into perspective (i) some very recent findings on the extraordinary biophysics and signaling properties of CNS miRNA in AD and aging human brain; (ii) how specific intrinsic biophysical attributes of miRNAs may play defining roles in the establishment, proliferation and spreading of the AD phenotype; and (iii) how miRNAs can serve as prospective therapeutic targets and biomarkers potentially useful in the clinical management of this terminal neurological disease whose incidence in our rapidly aging population is reaching epidemic proportions.

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Pathogenic microbes, the microbiome, and Alzheimer’s disease (AD)

Cited by 105 publications

References 59 publications

Analysis of RNA from Alzheimer’s Disease Post-mortem Brain Tissues

Analysis of RNA from Alzheimer’s Disease Post-mortem Brain Tissues

d-glutamate and Gut Microbiota in Alzheimer’s Disease

microRNA (miRNA)-Mediated Pathogenetic Signaling in Alzheimer’s Disease (AD)

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