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Disease ⇒ Alzheimer’s disease {40000139}

Record Keys


Type:
Disease
Definition:
Alzheimer’s disease
Parent:[  ]

Details


Initialisation date:
2020-09-06
Other Terms:
AD, ASD

Links


Meta Information


MedDra ID:
10012271
MedDra Level:
pt
ICD:[  ]
Category:
Neurology
Zone:[  ]
Mechanism:[  ]

Notes:


- The reference 1 with the title "We might have Alzheimer’s all wrong"



- daily oral administration of B. breve A1 > suppress the hippocampal expressions of inflammation and immune-reactive genes that are induced by amyloid-β > reduced the cognitive dysfunction normally induced by amyloid beta > significantly higher levels of acetate, but not propionate or butyrate.
- Butyrate activates the secretion of BDNF ( brain-derived neurotrophic factor) > ameloriate Coginitive dysfunction in AD.
- Enterobacteria infection > exacerbate the progression of AD.
- pro-inflammatory Clostridium Cluster I significantly correlated with anti-inflammatory Faecalibacterium prausnitzii.
- Amyloid positive patients showed higher levels of pro-inflammatory cytokines.

References Notes


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Shared Reference Notes


  • [1.4] [#Bifidobacterium breve] [#Probiotic
  • [1.22
    - Fungi in gut linked to higher Alzheimer’s risk can be reduced through ketogenic diet.
  • [1.23
    - Amyloid SUVR uptake is positively associated with - blood LPS - acetate and valerate - pro-inflammatory cytokines - biomarkers of endothelial dysfunction - Amyloid SUVR uptake is is negatively correlated with - butyrate - anti-inflammatory cytokine IL10 -Endothelial dysfunction is positively associated with - pro-inflammatory cytokines, acetate and valerate -Endothelial dysfunction is negatively associated with - butyrate and IL10 levels.
  • [1.24
    - The gut microbiome of AD participants has decreased microbial diversity. - Bacteroidetes are increased and Bifidobacterium and Firmicutes are decreased in the microbiome of AD participants. - Porphyromonas gingivalis, the keystone pathogen in chronic periodontitis, identified in the brain of Alzheimers disease patients. Toxic proteases from the bacterium called gingipains were also identified in the brain of Alzheimes patients, and levels correlated with tau and ubiquitin pathology. - Oral infections with Porphyromonas gingivalis, or introduction of its lipopolysaccharide (LPS), in various mouse models has demonstrated the development of key neuropathological hallmark lesions defining AD.
  • [1.25
    - Curli are cell surface amyloid proteins abundantly expressed by E. coli to exacerbate αSyn-induced behavioral deficits, including intestinal and motor impairments.
  • [1.26
    - Porphyromonas gingivalis, the keystone pathogen in chronic periodontitis, was identified in the brain of Alzheimer’s disease patients. Toxic proteases from the bacterium called gingipains were also identified in the brain of Alzheimer’s patients, and levels correlated with tau and ubiquitin pathology.
  • [1.27
    - Resveratrol has been proposed as a beneficial compound to delay ageing and cellular senescence.
  • [1.28
    - The gut microbiota-derived metabolite TMAO is elevated in the CSF of individuals with MCI and AD dementia, and that levels of CSF TMAO are associated with CSF biomarkers of AD pathology and neuronal degeneration.
  • [1.5
    - #Bifidobacterium breve, improves cognition. - The improvement of cognitive function reveal an inverse correlation of HbA1c with total RBANS score amelioration after the study only in the probiotic group.
  • [1.29
    - Increasing evidence points to several mitochondrial functions that are affected in AD. - Deficit in this mitochondrial may be at the heart of the progression of AD itself.
  • [1.30
    - Various gut microbes such as Actinobacteria, Bacteroidetes, E. coli, Firmicutes, Proteobacteria, Tenericutes, and Verrucomicrobia are known to play a crucial role in the pathogenesis of AD. - These microbes and their metabolites modulate various physiological processes that contribute to AD pathogenesis, such as neuroinflammation and other inflammatory processes, amyloid deposition, cytokine storm syndrome, altered BDNF and NMDA signaling, impairing neurodevelopmental processes. - Epigenetic markers associated with AD mainly include histone modifications and DNA methylation, which are under the direct control of a variety of enzymes, such as acetylases and methylases which activity is dependent upon the metabolites generated by the host’s gut microbiome.
  • [1.21] [#Poor oraly Health
    - At genera and species levels, higher subgingival periodontal dysbiosis was associated with reduced CSF amyloid beta (Aβ)42 but not with P‐tau.
  • [1.31
    - Colonization of the C. elegans gut with enteric bacterial pathogens disrupted proteostasis in the intestine, muscle, neurons, and the gonad. - The presence of bacteria that conditionally synthesize #Butyrate, a molecule previously shown to be beneficial in neurodegenerative disease models, suppressed aggregation and the associated proteotoxicity.
  • [1.32
    - The effects of gut microbiota in AD are mediated by microbial metabolites that either act on local neurons in the gut and surrounding tissues and send signals to the brain, and/or get absorbed from the gut and reach to brain through circulation. Such examples are monoamines, short-chain fatty acids (SCFAs), gamma-aminobutyric acid (GABA), beta-methylamino-L-alanine, brain-derived neurotrophic factor, serotonin, and dopamine
  • - Specific bacteria, for example, Escherichia coli, Bacillus subtilis, Salmonella typhimurium, and Salmonella enterica can also produce #Amyloids.
  • [#Keto diet] - MD-ketogenic diet improved the AD biomarkers viz. amyloid and tau proteins in the cerebrospinal fluids of MCI patients, wherein these changes linked with increased gut #Butyrate. - There is a significant reduction in Aβ levels and increase in behavioral responses after 12-weeks of sodium #Butyrate supplementation in mouse
  • - #Lipopolysaccharide (LPS), an outer cell wall component of Gram-negative bacteria that can be highly pro-inflammatory, can enhance Aβ accumulation in brain and induce cognitive dysfunction. - AD patients show higher LPS levels in blood plasma, and neocortex and hippocampus. - LPS can also cause chronic neuroinflammation, nerve cell death in entorhinal cortex, and impairment of synaptic plasticity of neurons in hippocampus.
  • [#Plant-based diet] - Oxidative stress can be modulated by diet, for example, high-fruit-and-vegetable diets improve cognition, which is linked with decreased oxidative stress in elderly;
  • - Patients with MCI and AD also show higher levels of gut microbiota-derived trimethylamine N-oxide (#TMAO) in the cerebrospinal fluid. - #TMAO correlate with AD biomarkers including pTau, total Tau, and Aβ42. - #TMAO treatment reduces cognitive function and aging signs in mice, by ameliorating neuronal senescence and mitochondrial dysfunction. - #TMAO and its precursors have inflammatory biomarkers, possibly contributing to AD-related leaky gut.
  • [#Western-style diet] - The Western diet consists of low-fiber, high-fat, and high-protein foods, where it is common to eat fatty red meats and eggs that are rich in TMA and choline, thus increase #TMAO production.
  • [1.19
    - The #ApoE4 allele is the most well-studied genetic risk factor for Alzheimer’s disease, a condition that is increasing in prevalence and remains without a cure. - Precision nutrition targeting metabolic pathways altered by ApoE4 provides a tool for the potential prevention of disease.
  • [1.34
    - AD elders had increased proportions of specific bacterial species that have associations with neurological disorders (including AD). These include Odoribacter splanchnicus, a bacterial species with genes that have been associated with the Alzheimers pathway (5) - Blautia were more abundant in AD patients. - Elevated GABA was potentially associated with a lower risk of AD. - Gut microbial neurotransmitter GABA, a downstream product of Blautia-dependent arginine metabolism, was related to a reduced risk of AD. - Lower levels of gut product of GABA were observed in patients with AD. - The biological mechanisms of GABA production include degradation of putrescine, decarboxylation of glutamate, or from arginine or ornithine. In - Blautia has a strong correlation with arginine metabolism, which may be involved in AD pathogenesis by regulating its downstream products such as GABA, supporting the potential pathway. - Elevated Enterobacteriales was also associated with a higher risk of ASD. - Gut microbiome may excrete large quantities of lipopolysaccharides and amyloids, resulting in the pathogenesis of AD during aging when the permeability of gastrointestinal tract epithelium or blood-brain barrier increases.
  • [1.35] [#Vitamin K2
  • [1.36] [#Fecal Microbiota Transplantation
  • [1.37
    - At the follow-up visit 2 months post-FMT, the patient’s wife reported improvements in the patient’s mental acuity and affect. The MMSE was re-administered by the gastroenterologist (and subsequently by the neurologist) and the patient scored 26, indicating normal cognition. Four months post-FMT, the patient reported continued improvement in memory, with no progression in symptoms. The patient now remembered his daughter’s birthday, which he had not been able to recall previously, and was able to correct the physician’s recollections of his symptoms. Six months post-FMT, the patient reported a marked improvement in mood, was more interactive, and showed more expressive affect.
  • [1.15
    - Reduction of #Glutamine > causally associated with occurrence of AD.
  • [1.39] [#Consuming Basil
  • - #Treatment with Rifamixin > significant reduction in serum neurofilament-light levels >significant increase in fecal phylum Firmicutes microbiota. #Treatment with Rifamixin > reduces Serum pTau181 and GFAP levels and non-significant downward trend in serum cytokine IL-6 and IL-13 levels. Increases in stool #Erysipelatoclostridium > correlated significantly with reductions in serum pTau 181 and serum GFAP.
  • [1.20
    - The enrichment of #Actinomyces meyeri > inversely associated with the age of first #Cannabis smoking. - Oral exposure of #Actinomyces meyeri > decreased global activity, increased macrophage infiltration, and increased β-amyloid protein production in the mouse brains.
  • [1.41] [#Carnitine
  • [1.17
    - There is a significant inverse relationship between the onset of Alzheimer’s disease/#Parkinson’s Disease (AD/PD) and #Cancer. - An increase in PIN1 expression is related to a delay in the onset age of sporadic AD, whereas a decrease in PIN1 expression is associated with a reduced risk of various #Cancers. - prostate, ovarian, and lung #Cancers show the greatest negative correlation with AD.
  • [#Colorectal cancer] - Serum #TMAO levels in AD/CRC patients are higher than those in healthy people, and its concentrations may be positively correlated with AD/cancer progression
  • [#Parkinson’s Disease] - #Tryptophan metabolites can cross the blood-brain barrier > activate #AHR to regulate astrocytes and reduce central nervous system inflammation in AD and PD
  • - Decrease in #Bacteroidetes and #Alloprevotella and increase in #Proteobacteria, #Verrucomicrobia, #Akkermansia, and #Desulfovibrio > improve short-term memory ability and cognitive level of AD mice
  • - Increasing the relative abundance of #Bacteroides and #Faecalibacterium may improve cognitive levels
  • - #Butyrate can reduce AD by affecting the #P-glycoprotein pathway
  • [#Hydrogen sulfide] - H2S > important signaling molecule in organisms > improve the progression of AD by enhancing Nrf2 > reduce the production of Aβ by inhibiting β secretase 1 (BACE1) > and protect neurons by maintaining mitochondrial function
  • [#Lipopolysaccharide] - LPS >amage the blood-brain barrier so that it can enter the brain > hinder the outflow of Aβ from cells > neuroinflammation and the accumulation of neuronal Aβ in AD > induce hyperphosphorylation of tau protein.
  • - #Mucispirillum and #Ruminiclostridium are enriched in AD model mice
  • [1.42
    - Absence of gut microbiota > prominent reduction of cerebral amyloid-β plaques and neurofibrillary tangles pathology - absence of gut microbiota > altered inflammatory pathway and insulin/IGF-1 signalling in hippocampus. - #Poly-unsaturated fatty acid metabolites identified by metabolomic analysis, and their oxidative enzymes were selectively elevated, corresponding with microglia activation and inflammation. - AD patients’ gut microbiome exacerbated AD pathologies in 3×Tg mice, associated with C/EBPβ/asparagine endopeptidase pathway activation and cognitive dysfunctions compared with healthy donors’ microbiota transplants.
  • [1.43] [#Serotonin (5-hydroxytryptamine)
  • [1.44] [#Fecal Microbiota Transplantation
  • - Prevotella_9, Bacteroides, and members of the Ruminococcaceae family were among the top most significantly differentially abundant taxa
  • [1.13
    - High ceramide levels > associated with insulin resistance, hypercholesterolemia, liver steatosis, and the formation of lipid rafts. - Some classes of #Ceramides in the blood increase the risk for late-onset Alzheimer’s disease, as they are neurotoxic and induce apoptosis . - #Bacteroidetes phylum can synthesize #Sphingolipids > human epithelial cells > #Ceramides
  • [1.14] [#Porphyromonas gingivalis
    - tau to be a target of gingipain proteolysis and suggested that tau pathology in AD brains may be caused by transneural spread of P. gingivalis, tau damage by gingipain proteolysis, and activation of human proteases. They also hypothesized that #Gingipains might be a driver of a compensatory increase in tau production of AD patients.
  • [1.11
    - #Verrucarin A, produced in #Myrothecium spp., showed 80% decrease in Aβ production. Furthermore, addition of #Mer-A2026A, produced in #Streptomyces pactum, showed increase in Aβ42/40 ratio at the low concentration, and decrease in Aβ production at the higher concentration.
  • [1.46] [#Chlamydia pneumoniae
    - Among different types of microbes, #Human immunodeficiency virus-1 (HIV-1), #Herpes simplex virus-1 (HSV-1), Chlamydia pneumonia, #Spirochetes and #Candida albicans are frequently detected in the brain of AD patients. - #Amyloid-beta protein has demonstrated to exhibit antimicrobial properties upon encountering these pathogens.
  • [1.16
    - Treatment with #Sodium oligomannate > as well as the recently approved aducanumab, provides hope that new therapeutics with novel mechanisms of action may provide disease-modifying effects and help slow disease progression in people with AD.
  • [1.47] [#Short Chain Fatty Acid
    - reduced levels of SCFAs were observed in patients with Alzheimer’s disease, and they also promoted #Depression-like behaviors and impairments of short-term memory in mice
  • [#Indole-3-propionic acid (IPA)] - indole-3-propionic acid has been shown to have neuroprotective and antioxidant effects, protecting primary neurons and neuroblastoma cells from oxidative damage and death caused by amyloid β protein (Aβ)
  • [1.48] [#Bacteroides fragilis] [#Amyloid-beta
    - Presence of #Amyloid deposits was associated with greater abundance of proinflammatory taxa (#Escherichia/#Shigella), which were in turn correlated with proinflammatory cytokines, and with reduced abundance of #Eubacterium rectale and B. fragilis, 2 taxa with anti-inflammatory activity
  • [#Helicobacter pylori] - Patients with the H. Pylori infection have been found to perform more poorly on the Mini–Mental State Examination, verbal memory tasks, and serial digit learning tasks; the infection causes inflammation and even tau hyperphosphorylation.
  • [1.10] [#Fusobacterium nucleatum] [#Amyloid-beta, #Lipopolysaccharide
    - antibodies to F. nucleatum can be detected in the serum of patients with AD or cognitive impairment. - F. nucleatum activates microglial cells causing morphological changes, accelerated proliferation and enhanced expression of TNF-α and IL-1β in microglial cells. - LPS promoted the proliferation of brain microglia - F. nucleatum-induced periodontitis resulted in the exacerbation of Alzheimer’s symptoms in 5XFAD mice including increased cognitive impairment, beta-amyloid accumulation and Tau protein phosphorylation in the mouse cerebrum. - The stimnuli like LPS, Aβ or IFN-γ would activate microglial M1 phenotype, leading to the expression of pro-inflammatory cytokines and irreversible neuron loss. - The main known virulence factors of F. nucleatum include FadA, Fap2, and LPS
  • [1.18
    - #Vitamin B12 deficiency at the brain level is associated with affective disorders, behavior changes, psychosis, cognitive impairment or decline, and #Dementia (including Alzheimer’s disease and vascular #Dementia protection)
  • [1.49
    - dementia-free older adults taking #Vitamin D3 supplements for over 146 days/year were 1.8 times more likely to develop dementia than those not taking the supplements. - supplementation of #Vitamin D led to increased Aβ deposition and exacerbated AD.
  • [1.8
    - beneficial bacteria such as Candidatus saccharimonas and Rikenellaceae decreased in APP/PS1 mice. Also, inflammatory or Aβ-associated bacteria such as Erysipelotrichaceae and Proteobacteria increased in APP/PS1 mice.
  • [#Bacillus firmus] - B. firmus, Rikenella, #Clostridium sp. Culture-27, and #Deoxyuridine, may play important roles in AD pathology.
  • - #Rikenella decreased in AD mice and was reversed in gut flora-targeted photobiomodulation therapy, indicating that #Rikenella may be a potential therapeutic target for AD.
  • [#Lipopolysaccharide] - #Bacteroides fragilis in the human gastrointestinal (GI) tract generates > neurotoxin #BF-LPS > #BF-LPS leaks out of the GI tract, crosses the blood brain barrier via the circulatory system, and accesses brain compartments > inreases inflammation in brain cells and inhibits neuron-specific neurofilament light (NF-L,) a protein that supports cell integrity > deficiency of NF-L > consequent atrophy of the neuronal cytoskeleton and the disruption of synaptic organization.
  • [#Lipopolysaccharide] - LPS and other pro-inflammatory stressors strongly induce a defined set of NF-kB (p50/p65)-sensitive human microRNAs, including a brain-enriched Homo sapien microRNA-30b-5p (hsa-miRNA-30b-5p; miRNA-30b) > upregulated in AD brain and LPS-stressed human neuronal-glial (HNG) cells in primary culture targets the neurofilament light (NF-L) chain mRNA 3’-untranslated region (3’-UTR) > post-transcriptional downregulation of NF-L expression observed within both AD and LPS-treated HNG cells > A deficiency of NF-L is associated with consequent atrophy of the neuronal cytoskeleton and the disruption of synaptic organization. - Increased miRNA-30b expression induces neuronal injury, neuron loss, neuronal inflammation, impairment of synaptic transmission, and synaptic failure in neurodegenerative disease and transgenic murine models.
  • [1.51
    - #Neisseria gonorrhoeae and Group B Streptococcus selectively bind huCD33 as part of immune evasive molecular mimicry of host SAMPs. - Human cells synthesize two forms of CD33: a full-length version and a mutated, inactive form that lacks the sugar-binding site. Those with a particular point mutation—different by a single changed nucleotide—produce a higher proportion of the mutant CD33, reducing the immune system’s ability to recognize #Sialic acids.
  • [1.52] [#Multiple Sclerosis, #Parkinson’s Disease] [#Short Chain Fatty Acid
    - SCFAs maintain the healthy mitochondrial function and stimulate the maturation of microglia, which consequently suppresses the progression of Neuro-Degenerative Diseases and cognitive decline by regulating inflammation and oxidative stress. - SCFAs functions as a cofactor for the host’s mitochondrial enzymes. - The properties of SCFAs depend on the G-protein coupled receptors (GPCR), histone deacetylases (HDAC) & peroxisome proliferator-activated receptor gamma (PPARγ) and regulatory T cells (Tregs) activation.
  • [1.53] [#Porphyromonas gingivalis] [#Amyloid-beta, #Gingipains
    - AβPP is an infection responsive protein cleaved via the amyloidogenic pathway on exposure to conditioned medium and in the presence of pro-inflammatory mediators.
  • [1.54] [#Porphyromonas gingivalis
    - nerve cells in the brain contain a type of protein called tau. When tau meets the #Gingipains enzyme, the tau released from the nerve cell. Once freed, tau physically changes, in the form of coils and non-coiling filaments. These filaments of tau then re-attach to the nerve cell and become incorporated into the lesion known as neurofibrillary tangles. - once a nerve cell dies and the free tau protein leaks into the brain, the tau may attach itself to healthy neighboring nerve cells, repeating the process and leading to further damage to the brain as the disease spreads
  • [1.55
    - AD elders were also depleted in Adlercreutzia equolifaciens, an equol-producing bacterium, which has beneficial effects in reducing experimental cutaneous inflammation in mice and the loss of which has been associated with the neurodegenerative disorder multiple sclerosis. - Bacteroides vulgatushe is a predictor of AD dementia which cause inflammatory states. - Increased proportions of Bacteroides, Alistipes, Odoribacter, and Barnesiella and decreased proportions of Lachnoclostridium were present in AD elders. - Increased proportions of Odoribacter and Barnesiella and decreased proportions of Eubacterium , Roseburia , Lachnoclostridium and Collinsella were seen in elders with other dementia types.

Common References