Amyloid-beta {90000281}

Shared Reference Notes

• [1.1] [#Alzheimer’s disease] [#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.
• [1.2] [#Alzheimer’s disease] [#Bacteroides fragilis] 
  - 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
• [1.3] [#Alzheimer’s disease] [#Fusobacterium nucleatum] [#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
• [1.4] [#Alzheimer’s disease] [#Porphyromonas gingivalis] [#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.
• [1.5] [#Alzheimer’s disease] 
  - many people accumulate amyloid plaques in the brain as they age, but only some of these people go on to develop dementia. - dementia symptoms may result not from the formation of insoluble plaques but from a lack of soluble amyloid beta protein.
• [1.6] [#Alzheimer’s disease] 
  - #Fusobacterium nucleatum can increased TNF-α and IL-1β expression in microglial cells, and also in vivo it can increase cognitive impairment, beta-amyloid accumulation and Tau protein phosphorylation in the cerebrum of an AD animal model.
• [1.7] 
  - #Chlamydia pneumoniae can infect the olfactory and trigeminal nerves, olfactory bulb and brain within 72 h in mice. - #Chlamydia pneumoniae infection also resulted in dysregulation of key pathways involved in #Alzheimer’s disease pathogenesis at 7 and 28 days after inoculation. - Amyloid beta accumulations were also detected adjacent to the #Chlamydia pneumoniae inclusions in the olfactory system. - Injury to the nasal epithelium resulted in increased peripheral nerve and olfactory bulb infection, but did not alter general CNS infection.
• [1.8] [#Alzheimer’s disease] [#Saccharomyces boulardii] [#Lipopolysaccharide] [#Probiotic] 
  - S. boulardii significantly reduced the elevated levels of serum interleukin (IL)-1β, IL-6, and tumor necrosis factor-α, as well as hippocampal levels of NLRP3 and caspase-1 in the LPS model. - S. boulardii alleviated amyloid-β deposition in the rat hippocampus. - S. boulardii could inhibit memory impairment, neuroinflammation, and amyloid-β accumulation induced by LPS, possibly by modifying the gut microbiota.
• [1.9] [#Alzheimer’s disease] [#Short Chain Fatty Acid] [#ApoE4 allele] 
  - Amyloid-Beta is a necessary factor in AD pathogenesis, its accumulation in and of itself is insufficient for neurodegeneration and cognitive decline. - pathological #Tau accumulation is closely linked with neurodegeneration and cognitive decline in AD and primary tauopathies. - apolipoprotein E (ApoE) isoforms, which strongly influence AD risk and regulate #Tau-mediated neurodegeneration, differentially affect the gut microbiota. - microbially produced short-chain fatty acids (SCFAs) are mediators of the neuroinflammation-neurodegeneration axis. - Supplementation of SCFAs to GF TE4 mice resulted in more reactive glial morphologies and gene expression as well as increased p-#Tau pathology.
• [#Alzheimer’s disease] - high-fat diets and #Obesity are associated with increased risk for developing AD and #Dementia. - the incidence of AD is higher in countries that typically consume high-fat diets as opposed to low-fat diets. - Increased Aβ plaques in the brain after consumption of a #High Fat Diet has been observed in mouse models of amyloidosis. - a high-fat diet can result in an increase in neuroinflammation and decreased performance on AD-related behavior tests.
• [#Alzheimer’s disease] - All humans produce Aβ40 and Aβ42 throughout life and levels of these proteins are relatively high in both the CSF and serum throughout life. - Aβ plaques can be present in cognitively normal individuals. This suggests that perhaps Aβ is present for a reason and serves a beneficial physiologic purpose in the human body. - Several bacteria and viruses > enhance amyloidogenic processing and subsequent Aβ production. - Aβ plaques in humans contain viral and bacterial DNA. - Aβ have similar structure to other antimicrobial peptides. - Aβ protects against infection in mouse, cell culture, and C elegans models. - Perhaps Aβ is initially increasingly produced as a response to real or perceived brain infection, but too much Aβ production eventually becomes detrimental by inducing neuronal toxicity, excessive neuroinflammation, and pathological tau seeding.
• [#Alzheimer’s disease] - levels of Aβ are increased when mice and human are awake and decrease when they are asleep. - These diurnal oscillations in Aβ levels in brain ISF are dissipated and the #Sleep–wake cycle is disrupted after Aβ plaque formation in the APP/PS1 mouse model of amyloidosis. - amelioration of Aβ plaque pathology with Aβ immunotherapy restored a normal #Sleep wake cycle and diurnal oscillations in Aβ levels in the mice. - Lower neuronal activity during #Sleep likely leads to less Aβ production.
• - higher #Mediterranean diet adherence led to higher grey matter volume, better memory, lower Aβ, and lower phosphorylated tau
• [1.11] [#Alzheimer’s disease] 
  - adding #Cinnamon or cinnamaldehyde to a cell medium can reduce #Tau aggregation, Amyloid β and increase cell viability. - #Cinnamon might be useful for preventing and reducing cognitive function impairment.
• [1.12] [#Alzheimer’s disease] [#Grape seed] 
  - the production of bioactive #Phenolic acids derived from the anthocyanin-rich GSPE is dependent on the microbiota, and two of the microbiota-derived metabolites 3-hydroxybenzoic acid and 3-(3′-hydroxyphenyl) #Propionic acid accumulate in micromolar concentrations in the brain where they can interfere with the assembly of amyloid-beta peptides.
• [#Epigallocatechin gallate] - a #Pomegranate extract was shown to reduce microgliosis and amyloid-beta plaque deposition in association with reduced #Anxiety-like behavior and increased memory performance. - This effect was attributed to two polyphenolic compounds, #Punicalagin and #Ellagic acid, and likely its bioactive microbial-derived metabolite EGCG
• [1.13] 
  - In the mice study, the increased abundance of #Lachnospiraceae family was associated with reduced deposition of β #Amyloid in brain tissue
• [1.14] [#Alzheimer’s disease] [#Phenolic acids] [#Olive] 
  - oral administration of EVOO and specific EVOO phenolic compounds, in particular, can reduce the accumulation of β-#Amyloid (Aβ) deposits and tau neuropathologies in mouse models of AD, resulting in improved memory and cognition.
• [1.15] [#Alzheimer’s disease] 
  - Aβ was associated with increased plasma phosphorylated tau and #Cognitive impairment only in those who tested positive for astrocyte reactivity (Ast+).
• [1.16] [#Alzheimer’s disease] 
  - #Cocoa extracts are effective in preventing the oligomerization of Aβ, with Lavado extract being most effective.
• [1.17] [#Alzheimer’s disease] 
  - #Spermidine-induced autophagy slows the rate of cognitive decline due to its ability to clear amyloid-beta plaques in the brain.
• [1.18] [#Alzheimer’s disease] [#Fasting] 
  - TRF (time-restricted feeding) had the remarkable capability of simultaneously reducing #Amyloid deposition, increasing Aβ42 clearance, improving #Sleep and memory, and normalizing daily transcription patterns of multiple genes, including those associated with AD and neuroinflammation. - TRF had a major impact on neuropathology, with treated APP23 TG mice displaying a significant reduction in plaque burden and #Amyloid deposition and a reversal of circulating biomarkers of AD. - TRF protocol was effective in reducing #Amyloid burden and improving memory in the APP knockin (APP-KI) mouse model.
• [1.19] [#Alzheimer’s disease] 
  - supplementation of #Acetate to the diet of a mouse model for AD induced the pro-inflammatory phenotype of microglia with elevated cytokine expression > suppress the phagocytosis by microglia in the presence of Aβ.
• - The #Mediterranean diet > improvement in memory, an increase in Aβ42:Aβ40, and pTau181 > protective lifestyle factor against #Dementia
• [#Alzheimer’s disease] - #Tryptophan metabolites have been shown to regulate the cerebral activity of #Neprilysin, a metalloproteinase that controls the degradation and clearance of Aβ peptides in the brain.
• [1.21] [#Actinomyces meyeri, #Actinomyces odontolyticus] 
  - oral inoculation of A. meyeri, as opposed to A. odontolyticus and #Neisseria elongate, led to proinflammatory myeloid cell infiltration in the brain (associated with long-term memory decline) and a robust increase in cortical Aβ plaques (averaging a 120% increase) in C57/B6 mice
• [#Alzheimer’s disease] [#Aggregatibacter actinomycetemcomitans] [#Lipopolysaccharide] - LPS from serotype B of A. actinomycetemcomitans, > trigger high levels of proinflammatory cytokine production in microglia and an increase the secretion of the Aβ1-42 peptide > AD
• [#Porphyromonas gingivalis] - the human neuroblastoma cell line SH-SY5Y produced Aβ40 and Aβ42 in response to P. gingivalis, which occurred through the cleavage of the #Amyloid-β protein precursor in vitro
• [#Treponema denticola] - oral inoculation of T. denticola into C57BL/6 mice has been shown to result in the production of Aβ1–42 in the hippocampus and neuronal apoptosis
• [1.22] [#Alzheimer’s disease, #Blood Brain Barrier Integrity] [#Candida albicans] 
  - C. albicans enters the mouse brain from the blood and induces two neuroimmune sensing mechanisms involving secreted #Aspartic proteinases (Saps) and #Candidalysin. - Saps disrupt tight junction proteins of the blood-brain barrier (BBB) to permit fungal brain invasion. - Saps also hydrolyze amyloid precursor protein (APP) into amyloid b (Ab)-like peptides that bind to Toll-like receptor 4 (TLR4) and promote fungal killing in vitro while #Candidalysin engages the integrin CD11b (Mac-1) on microglia.
• [1.23] [#Alzheimer’s disease] 
  - Early stage ovariectomy (OVX) leads to a reduction of plasma #Estradiol that is correlated with a significant alteration of gut microbiome composition and reduction in Aβ pathology. - supplementation of OVX-treated animals with #Estradiol restores Aβ burden and influences gut microbiome composition.
• [1.24] 
  - a deficiency in #Vitamin A leads to an elevation in serum pro-inflammatory cytokines TNF-α, IL-1β, and #IL-6 in APP/PS1 mice. - supplementation of #Vitamin A results in a decrease in these cytokines. - TNF-α has the ability to stimulate γ-secretase activity, which subsequently leads to an increased synthesis of Aβ peptides
• [#Cognitive impairment] - 12-week #Vitamin A-deficient diet resulted in decreased serum retinol levels, impaired cognition, and increased Aβ pathologies in the hippocampus of APP/PS1 mice.
• [#Cognitive impairment] - a #Vitamin A-enriched diet led to higher serum retinol levels, preserved cognition, and reduced Aβ pathologies in the hippocampus of APP/PS1 mice.
• [1.25] [#Short Chain Fatty Acid] 
  - supplementation of SCFAs simulated the role of the microbiota and increased Aβ plaque burden
• - #Tauroursodeoxycholic acid (TUDCA) reduces Aβ deposition, inhibits the progression of amyloid pathology and suppresses GSK3β activity, thereby reducing #Tau hyperphosphorylation and microglial cell activation. - TUDCA can bind to the G protein-coupled bile acid receptor 1/Takeda G protein-coupled receptor 5 (GPBAR1/TGR5) in microglial cells, increasing cAMP levels, inducing an anti-inflammatory phenotype of microglial cells, and attenuating inflammatory response
• [1.26] [#Alzheimer’s disease] 
  - neuritin (NRN1), a neurotrophic factor previously linked to cognitive resilience > provided dendritic spine resilience against amyloid-β (Aβ) and blocked Aβ-induced neuronal hyperexcitability in cultured neurons.

References Notes