Microglia in neurodegeneration

In the paper

“Microglia constitute 5–12% of CNS cells, depending on the region9.”

What the sources say

• Not checked yetcites [9] Lawson, L. J., Perry, V. H., Dri, P. & Gordon, S. Heterogeneity in the distribution and morphology of microglia in the normal adult mouse brain. Neuroscience 39, 151–170 (1990). source

In the paper

“They are the principal resident immune cells of the brain and are involved in homeostasis and in host defense against pathogens and CNS disorders10,11.”

What the sources say

• Not checked yetcites [10] El Khoury, J. Neurodegeneration and the neuroimmune system. Nat. Med. 16, 1369–1370 (2010). source
• Not checked yetcites [11] Ransohoff, R. M. & El Khoury, J. Microglia in health and disease. Cold Spring Harb. Perspect. Biol. 8, a020560 (2015). source

In the paper

“Ontological studies of microglia confirmed Hortega’s suspicion that they are mesenchymal, myeloid12, originating in the yolk sac, and capable of self-renewal independent of hematopoietic stem cells13.”

What the sources say

• Not checked yetcites [12] Kierdorf, K. et al. Microglia emerge from erythromyeloid precursors via Pu.1- and Irf8-dependent pathways. Nat. Neurosci. 16, 273–280 (2013). source
• Not checked yetcites [13] Tay, T. L. et al. A new fate mapping system reveals context-dependent random or clonal expansion of microglia. Nat. Neurosci. 20, 793–803 (2017). source

In the paper

“Microglial survival and maintenance depend on cytokines, including CSF1 and interleukin (IL)-3414, and on transcription factors such as IRF812.”

What the sources say

• Not checked yetcites [14] Wang, Y. et al. IL-34 is a tissue-restricted ligand of CSF1R required for the development of Langerhans cells and microglia. Nat. Immunol. 13, 753–760 (2012). source
• Not checked yetcites [12] Kierdorf, K. et al. Microglia emerge from erythromyeloid precursors via Pu.1- and Irf8-dependent pathways. Nat. Neurosci. 16, 273–280 (2013). source

In the paper

“Microglial transcriptomes allow them to perform three essential functions: (i) sense their environment, (ii) conduct physiological housekeeping, and (iii) protect against modified-self and non-self injurious agents.”

In the paper

“Based on these findings, microglial–Aβ interaction is a double-edged sword. While monitoring the brain environment, microglial sensing of Aβ peptides results in Aβ clearance and removal of the injurious agent (Fig. 3). However, persistent production of Aβ and its chronic interaction with microglia drive further amyloid deposition.”

In the paper

“Tauopathies are neurodegenerative diseases characterized by hyperphosphorylated and aggregated tau and neurofibrillary tangles.”

In the paper

“Interacting with astrocytes is another important microglial function involved in homeostasis, inflammation, and possibly neurodegeneration26.”

What the sources say

• Not checked yetcites [26] Liddelow, S. A. et al. Neurotoxic reactive astrocytes are induced by activated microglia. Nature 541, 481–487 (2017). source

In the paper

“Their thin processes are dynamic and in constant motion, allowing them to scan the area surrounding their cell body every few hours and rapidly polarize toward focal injury (Fig. 1a–c and Supplementary Video 1).”

In the paper

“In contrast, when activated, proinflammatory microglia increase tau phosphorylation50 and drive the spread of tau pathology48.”

What the sources say

• Not checked yetcites [50] Lee, D. C. et al. LPS- induced inflammation exacerbates phospho-tau pathology in rTg4510 mice. J. Neuroinflammation 7, 56 (2010). source
• Not checked yetcites [48] Asai, H. et al. Depletion of microglia and inhibition of exosome synthesis halt tau propagation. Nat. Neurosci. 18, 1584–1593 (2015). source

In the paper

“Aβ deposition is regulated by equilibrium between Aβ production and clearance. Small changes in this equilibrium result in abnormal accumulation.”

In the paper

“These findings support a direct link between aberrant microglial functions and AD and suggest that a subset of microglia transition from a homeostatic to DAMs in AD.”

In the paper

“They use the products of nearly 100 genes to sense changes in their microenvironment (their sensome) including P2yr12, AXL, and MER4,7,19”

What the sources say

• Not checked yetcites [4] Haynes, S. E. et al. The P2Y12 receptor regulates microglial activation by extracellular nucleotides. Nat. Neurosci. 9, 1512–1519 (2006). source
• Not checked yetcites [7] Hickman, S. E. et al. The microglial sensome revealed by direct RNA sequencing. Nat. Neurosci. 16, 1896–1905 (2013). source
• Not checked yetcites [19] Fourgeaud, L. et al. TAM receptors regulate multiple features of microglial physiology. Nature 532, 240–244 (2016). source

In the paper

“Alzheimer’s disease (AD) is characterized by formation of Aβ-containing plaques, neurofibrillary tangles comprising intracellular hyperphosphorylated tau protein, and neuronal loss29.”

What the sources say

• Not checked yetcites [29] Selkoe, D. J. & Hardy, J. The amyloid hypothesis of Alzheimer’s disease at 25 years. EMBO Mol. Med. 8, 595–608 (2016). source

In the paper

“Microglia–Aβ interactions lead to early synapse loss39, production of neurotoxic reactive oxygen and nitrogen species (ROS and RNS), NLRP3 inflammasome activation, and production of proinflammatory cytokines and TNF27,40–42.”

What the sources say

• Not checked yetcites [39] Hong, S. et al. Complement and microglia mediate early synapse loss in Alzheimer mouse models. Science 352, 712–716 (2016). source
• Not checked yetcites [27] El Khoury, J. B. et al. CD36 mediates the innate host response to beta-amyloid. J. Exp. Med. 197, 1657–1666 (2003). source
• Not checked yetcites [40] Coraci, I. S. et al. CD36, a class B scavenger receptor, is expressed on microglia in Alzheimer’s disease brains and can mediate production of reactive oxygen species in response to beta-amyloid fibrils. Am. J. Pathol. 160, 101–112 (2002). source
• Not checked yetcites [41] Gold, M. & El Khoury, J. β-amyloid, microglia, and the inflammasome in Alzheimer’s disease. Semin. Immunopathol. 37, 607–611 (2015). source
• Not checked yetcites [42] Venegas, C. et al. Microglia-derived ASC specks cross-seed amyloid-β in Alzheimer’s disease. Nature 552, 355–361 (2017). source

In the paper

“Sensome mRNAs are uniformly expressed in microglia in various areas of the brain, suggesting that all microglia are capable of performing their sensing function (Fig. 1e).”

In the paper

“Similarly, Aβ-induced cytokines promote tau hyperphosphorylation and pathology, thus initiating a self-perpetuating loop that culminates in worsening disease44,45.”

What the sources say

• Not checked yetcites [44] Oddo, S., Caccamo, A., Kitazawa, M., Tseng, B. P. & LaFerla, F. M. Amyloid deposition precedes tangle formation in a triple transgenic model of Alzheimer’s disease. Neurobiol. Aging 24, 1063–1070 (2003). source
• Not checked yetcites [45] Villemagne, V. L. et al. Aβ-amyloid and tau imaging in dementia. Semin. Nucl. Med. 47, 75–88 (2017). source

In the paper

“Physiological housekeeping functions include synaptic remodeling (a function critical for CNS development, homeostasis, and neurodegeneration20–22), migration to sites of neuronal death to phagocytose dead or dying cells23,24 or debris, and maintaining myelin homeostasis25.”

What the sources say

• Not checked yetcites [20] Vasek, M. J. et al. A complement-microglial axis drives synapse loss during virus-induced memory impairment. Nature 534, 538–543 (2016). source
• Not checked yetcites [21] Lui, H. et al. Progranulin deficiency promotes circuit-specific synaptic pruning by microglia via complement activation. Cell 165, 921–935 (2016). source
• Not checked yetcites [22] Zhan, Y. et al. Deficient neuron-microglia signaling results in impaired functional brain connectivity and social behavior. Nat. Neurosci. 17, 400–406 (2014). source
• Not checked yetcites [23] Fuhrmann, M. et al. Microglial Cx3cr1 knockout prevents neuron loss in a mouse model of Alzheimer’s disease. Nat. Neurosci. 13, 411–413 (2010). source
• Not checked yetcites [24] Krasemann, S. et al. The TREM2-APOE pathway drives the transcriptional phenotype of dysfunctional microglia in neurodegenerative diseases. Immunity 47, 566–581.e9 (2017). source
• Not checked yetcites [25] Healy, L. M. et al. MerTK is a functional regulator of myelin phagocytosis by human myeloid cells. J. Immunol. 196, 3375–3384 (2016). source

In the paper

“Most tauopathies have neuronal and glial accumulations of toxic insoluble tau, neuronal loss, and proinflammatory microglia47.”

What the sources say

• Not checked yetcites [47] Ferrer, I. et al. Glial and neuronal tau pathology in tauopathies: characterization of disease-specific phenotypes and tau pathology progression. J. Neuropathol. Exp. Neurol. 73, 81–97 (2014). source

In the paper

“DAMs are located around Aβ plaques and have dysregulated expression of sensing, housekeeping, and host-defense genes.”

In the paper

“They contain intracellular Aβ, suggesting phagocytosis31, show proinflammatory morphological changes such as somatic swelling and process shortening (Fig. 2c), and have increased proinflammatory markers including major histocompatibility complex II, CD36, IL-1, IL-6, and TNF32,33.”

What the sources say

• Not checked yetcites [31] D’Andrea, M. R., Cole, G. M. & Ard, M. D. The microglial phagocytic role with specific plaque types in the Alzheimer disease brain. Neurobiol. Aging 25, 675–683 (2004). source
• Not checked yetcites [32] Tooyama, I., Kimura, H., Akiyama, H. & McGeer, P. L. Reactive microglia express class I and class II major histocompatibility complex antigens in Alzheimer’s disease. Brain Res. 523, 273–280 (1990). source
• Not checked yetcites [33] Martin, E., Boucher, C., Fontaine, B. & Delarasse, C. Distinct inflammatory phenotypes of microglia and monocyte-derived macrophages in Alzheimer’s disease models: effects of aging and amyloid pathology. Aging Cell 16, 27–38 (2017). source

In the paper

“Microglia can engulf, degrade, and clear tau48,49.”

What the sources say

• Not checked yetcites [48] Asai, H. et al. Depletion of microglia and inhibition of exosome synthesis halt tau propagation. Nat. Neurosci. 18, 1584–1593 (2015). source
• Not checked yetcites [49] Bolós, M. et al. Direct evidence of internalization of tau by microglia in vitro and in vivo. J. Alzheimers Dis. 50, 77–87 (2016). source

In the paper

“Proinflammatory microglia precede visible tau pathology in transgenic mice, and their activation is attenuated by the immunosuppressant drug FK506, which attenuates tau pathology and extends lifespan in these mice, suggesting that microglia can mediate tau neurotoxicity54.”

What the sources say

• Not checked yetcites [54] Yoshiyama, Y. et al. Synapse loss and microglial activation precede tangles in a P301S tauopathy mouse model. Neuron 53, 337–351 (2007). source

In the paper

“Indeed, Aβ-induced proinflammatory cytokines reduce microglial Aβ clearance ability, and NLRP3 activation releases microglial apoptosis-associated speck-like protein containing a CARD (ASC) which binds Aβ, causing its aggregation and leading to further amyloid ‘seeding’ and spreading of amyloid pathology42.”

What the sources say

• Not checked yetcites [42] Venegas, C. et al. Microglia-derived ASC specks cross-seed amyloid-β in Alzheimer’s disease. Nature 552, 355–361 (2017). source

In the paper

“Persistent neuroinflammation in turn induces neurotoxicity, leading to neurodegeneration.”

In the paper

“Microglia mediate host defense against infectious pathogens, injurious self-proteins such as Aβ, aggregated α-synuclein, mutant huntingtin, mutant or oxidized superoxide dismutase (SOD), or prions, as well as primary or metastatic CNS tumors.”

In the paper

“microglia from a mouse model of Aβ deposition (Aβ-mice) have reduced expression of Aβ-phagocytic receptors and Aβ-degrading enzymes, but their ability to produce proinflammatory cytokines was maintained6.”

What the sources say

• Not checked yetcites [6] Hickman, S. E., Allison, E. K. & El Khoury, J. Microglial dysfunction and defective beta-amyloid clearance pathways in aging Alzheimer’s disease mice. J. Neurosci. 28, 8354–8360 (2008). source

In the paper

“A take-home message is that there are no resting microglia (Fig. 2). Their sensing, housekeeping, and protecting functions keep them constantly engaged, and most microglia in healthy brains are capable of performing such functions.”

In the paper

“Aβ clearance involves, in part36, phagocytosis and endocytosis via microglial scavenger receptors (SRs)37,38 and extracellular degradation by Aβ-degrading enzymes6,36.”

What the sources say

• Not checked yetcites [36] El Khoury, J. & Hickman, S.E. Mechanisms of amyloid-beta clearance in Alzheimer’s disease. in Research Progress in Alzheimer’s Disease and Dementia, vol. 4. (ed. Sun, M.-K.) 37–66 (Nova Science Publishers, Hauppauge, NY, USA, 2009).
• Not checked yetcites [37] Frenkel, D. et al. Scara1 deficiency impairs clearance of soluble amyloid-β by mononuclear phagocytes and accelerates Alzheimer’s-like disease progression. Nat. Commun. 4, 2030 (2013). source
• Not checked yetcites [38] El Khoury, J. et al. Scavenger receptor-mediated adhesion of microglia to beta-amyloid fibrils. Nature 382, 716–719 (1996). source
• Not checked yetcites [6] Hickman, S. E., Allison, E. K. & El Khoury, J. Microglial dysfunction and defective beta-amyloid clearance pathways in aging Alzheimer’s disease mice. J. Neurosci. 28, 8354–8360 (2008). source

In the paper

“In response to such stimuli, microglia can initiate a neuroinflammatory response which, like peripheral inflammation, includes production of cytokines such as TNF and IL-16,27, and possibly chemokines such as Ccl228, to recruit additional cells and induce them to clear injurious agents and maintain brain homeostasis.”

What the sources say

• Not checked yetcites [6] Hickman, S. E., Allison, E. K. & El Khoury, J. Microglial dysfunction and defective beta-amyloid clearance pathways in aging Alzheimer’s disease mice. J. Neurosci. 28, 8354–8360 (2008). source
• Not checked yetcites [27] El Khoury, J. B. et al. CD36 mediates the innate host response to beta-amyloid. J. Exp. Med. 197, 1657–1666 (2003). source
• Not checked yetcites [28] El Khoury, J. et al. Ccr2 deficiency impairs microglial accumulation and accelerates progression of Alzheimer-like disease. Nat. Med. 13, 432–438 (2007). source

In the paper

“Neurodegeneration occurs in the substantia nigra, with dopaminergic denervation of the striatum and accumulation of Lewy bodies containing aggregated α-synuclein59.”

What the sources say

• Not checked yetcites [59] Dickson, D. W. Neuropathology of Parkinson disease. Parkinsonism Relat. Disord. 46(Suppl 1), S30–S33 (2018). source

In the paper

“Parkinson’s disease (PD) is the second most common neurodegenerative disease, affecting 1.2% of individuals over age 65. Most cases are sporadic and 5–10% are inherited58.”

What the sources say

• Not checked yetcites [58] Deng, H., Wang, P. & Jankovic, J. The genetics of Parkinson disease. Ageing Res. Rev. 42, 72–85 (2018). source

In the paper

“However, at disease onset, microglia promote axonal regeneration, remyelination, clearance of inhibitory myelin debris, and the release of neurotrophic factors, suggesting a beneficial role67.”

What the sources say

• Not checked yetcites [67] Yamasaki, R. et al. Differential roles of microglia and monocytes in the inflamed central nervous system. J. Exp. Med. 211, 1533–1549 (2014). source

In the paper

“Microglia accumulate near α-synuclein deposits and become proinflammatory in a manner dependent on receptors that also bind Aβ, such as CD36 and TLR263–65.”

What the sources say

• Not checked yetcites [63] Croisier, E., Moran, L. B., Dexter, D. T., Pearce, R. K. & Graeber, M. B. Microglial inflammation in the parkinsonian substantia nigra: relationship to alpha-synuclein deposition. J. Neuroinflammation 2, 14 (2005). source
• Not checked yetcites [64] Su, X. et al. Synuclein activates microglia in a model of Parkinson’s disease. Neurobiol. Aging 29, 1690–1701 (2008). source
• Not checked yetcites [65] Kim, C. et al. Neuron-released oligomeric α-synuclein is an endogenous agonist of TLR2 for paracrine activation of microglia. Nat. Commun. 4, 1562 (2013). source

In the paper

“In experimental autoimmune encephalomyelitis (EAE), a mouse model of MS, microglia release proteases, proinflammatory cytokines, ROS, and RNS, and they recruit reactive T lymphocytes, thereby causing toxicity to neurons and oligodendrocyte precursors.”

In the paper

“What is clear is that essential microglial functions are altered in EAE and possibly in MS, including their ability to sense and clear debris and mount a neuroprotective response.”

In the paper

“In Aβ-mice, progranulin overexpression inhibits Aβ deposition and protects from Aβ toxicity.”

What the sources say

• Not checked yetcites [144] Minami, S. S. et al. Progranulin protects against amyloid β deposition and toxicity in Alzheimer’s disease mouse models. Nat. Med. 20, 1157–1164 (2014). source

In the paper

“However, no change in cognition or microglial recruitment to plaques was seen in 12-month-old mice”

What the sources say

• Not checked yetcites [140] Vodopivec, I. et al. RAGE does not affect amyloid pathology in transgenic ArcAbeta mice. Neurodegener. Dis. 6, 270–280 (2009). source

In the paper

“SR-B2 promotes α-synuclein–microglial interactions64 and senses misfolded mutant or oxidized SOD1 in diseased motor neurons or in the extracellular space, rendering these cells proinflammatory85.”

What the sources say

• Not checked yetcites [64] Su, X. et al. Synuclein activates microglia in a model of Parkinson’s disease. Neurobiol. Aging 29, 1690–1701 (2008). source
• Not checked yetcites [85] Zhao, W. et al. Extracellular mutant SOD1 induces microglial-mediated motoneuron injury. Glia 58, 231–243 (2010). source

In the paper

“whereas blocking CD36– or RAGE–Aβ interactions or reducing expression of these SRs may stop or delay AD progression.”

In the paper

“SR-A1-deficiency decreases microglial Aβ uptake by 60%37,136 and increases mortality and Aβ accumulation37,136”

What the sources say

• Not checked yetcites [37] Frenkel, D. et al. Scara1 deficiency impairs clearance of soluble amyloid-β by mononuclear phagocytes and accelerates Alzheimer’s-like disease progression. Nat. Commun. 4, 2030 (2013). source
• Not checked yetcites [136] Cornejo, F. et al. Scavenger receptor-A deficiency impairs immune response of microglia and astrocytes potentiating Alzheimer’s disease pathophysiology. Brain Behav. Immun. 69, 336–350 (2018). source

In the paper

“Selective reduction of microglial expression of progranulin in Aβ-mice also impairs phagocytosis, increases plaque load, and exacerbates cognitive deficits.”

What the sources say

• Not checked yetcites [144] Minami, S. S. et al. Progranulin protects against amyloid β deposition and toxicity in Alzheimer’s disease mouse models. Nat. Med. 20, 1157–1164 (2014). source

In the paper

“Because of their ability to bind a diverse class of ligands, SRs are important sensors of misfolded proteins including Aβ, mSOD1, aggregated α-synuclein, and PrPsc, possibly to clear them.”

In the paper

“Multiple sclerosis (MS) patients have demyelinated plaques in the white and gray matter. Ongoing disease leads to progressive neurodegeneration, resulting in brain atrophy.”

In the paper

“Binding of Aβ to the microglial SR-J1 (also called RAGE) activates MAPK and NF-κB and contributes to synaptic dysfunction through IL-1β release in 2- to 3-month-old animals139.”

What the sources say

• Not checked yetcites [139] Origlia, N. et al. Microglial receptor for advanced glycation end product-dependent signal pathway drives beta-amyloid-induced synaptic depression and long-term depression impairment in entorhinal cortex. J. Neurosci. 30, 11414–11425 (2010). source

In the paper

“Some of these receptors, such as CD36, form receptor complexes with other PRRS such as TLRs and initiate an inflammatory response that leads to neurotoxicity and neurodegeneration.”

In the paper

“Huntington’s disease (HD) is characterized by progressive atrophy of the striatum and cortex in advanced disease69.”

What the sources say

• Not checked yetcites [69] Ghosh, R. & Tabrizi, S. J. Huntington disease. Handb. Clin. Neurol. 147, 255–278 (2018). source

In the paper

“Positron-emission tomography (PET) studies show widespread proinflammatory microglia, but this response does not correlate with clinical severity, suggesting it occurs early in the disease61.”

What the sources say

• Not checked yetcites [61] Gerhard, A. et al. In vivo imaging of microglial activation with [11C](R)-PK11195 PET in idiopathic Parkinson’s disease. Neurobiol. Dis. 21, 404–412 (2006). source

In the paper

“Progranulin deficiency leads to age-dependent, progressive upregulation of lysosomal and innate immunity genes, increased complement production, and enhanced C1q-dependent synaptic pruning by microglia”

What the sources say

• Not checked yetcites [21] Lui, H. et al. Progranulin deficiency promotes circuit-specific synaptic pruning by microglia via complement activation. Cell 165, 921–935 (2016). source

In the paper

“These findings, which need to be validated in animal models of PD, suggest that AD and PD have similar pathogenic pathways, raising the possibility that microglia may also be a double-edged sword in PD.”

In the paper

“Microglia first sense and clear tau in an attempt to protect from tau toxicity, but dysregulation of microglial sensing and housekeeping pathways, such as the Cx3cr1 and Trem2 pathways, lead to dysregulation of the host-defense pathway, resulting in a neuroinflammatory response gone awry, causing neuronal damage and loss55–57.”

What the sources say

• Not checked yetcites [55] Bhaskar, K. et al. Regulation of tau pathology by the microglial fractalkine receptor. Neuron 68, 19–31 (2010). source
• Not checked yetcites [56] Nash, K. R. et al. Fractalkine overexpression suppresses tau pathology in a mouse model of tauopathy. Neurobiol. Aging 34, 1540–1548 (2013). source
• Not checked yetcites [57] Bemiller, S. M. et al. TREM2 deficiency exacerbates tau pathology through dysregulated kinase signaling in a mouse model of tauopathy. Mol. Neurodegener. 12, 74 (2017). source

In the paper

“Neuroinflammation is present in all stages of MS, and a proposed classification of MS lesions relies in part on the presence or absence of microglia in the lesions66.”

What the sources say

• Not checked yetcites [66] Kuhlmann, T. et al. An updated histological classification system for multiple sclerosis lesions. Acta Neuropathol. 133, 13–24 (2017). source

In the paper

“These reports indicate that various SRs play complementary roles in microglia–Aβ interactions that may have therapeutic implications for AD.”

In the paper

“In the MPTP mouse model of PD, upregulation of progranulin expression in nigrostriatal neurons was accompanied by reductions in markers of MPTP-induced inflammation and apoptosis, and it protected these neurons from MPTP toxicity and preserved striatal dopamine content and turnover.”

What the sources say

• Not checked yetcites [145] Van Kampen, J. M., Baranowski, D. & Kay, D. G. Progranulin gene delivery protects dopaminergic neurons in a mouse model of Parkinson’s disease. PLoS One 9, e97032 (2014). source

In the paper

“Progranulin is a secreted glycoprotein with neuro-immunomodulatory properties and autocrine neurotrophic functions important for long-term neuronal survival141.”

What the sources say

• Not checked yetcites [141] Chitramuthu, B. P., Bennett, H. P. J. & Bateman, A. Progranulin: a new avenue towards the understanding and treatment of neurodegenerative disease. Brain 140, 3081–3104 (2017). source

In the paper

“Six-monthold RAGE−/− Aβ-mice have reduced Aβ deposition and more Aβ-degrading enzymes140.”

What the sources say

• Not checked yetcites [140] Vodopivec, I. et al. RAGE does not affect amyloid pathology in transgenic ArcAbeta mice. Neurodegener. Dis. 6, 270–280 (2009). source

In the paper

“Microglia internalize and degrade α-synuclein, possibly to clear it. A defect in this process leads to accumulation of extracellular α-synuclein similar to Aβ62.”

What the sources say

• Not checked yetcites [62] Halliday, G. M. & Stevens, C. H. Glia: initiators and progressors of pathology in Parkinson’s disease. Mov. Disord. 26, 6–17 (2011). source

In the paper

“SR-B2 (also called CD36) is also a microglial Aβ receptor that forms a complex with TLR-4 and TLR-6, leading to cytokine, chemokine, and ROS production, as well as microglial migration, inflammasome activation, and neurotoxicity27,40.”

What the sources say

• Not checked yetcites [27] El Khoury, J. B. et al. CD36 mediates the innate host response to beta-amyloid. J. Exp. Med. 197, 1657–1666 (2003). source
• Not checked yetcites [40] Coraci, I. S. et al. CD36, a class B scavenger receptor, is expressed on microglia in Alzheimer’s disease brains and can mediate production of reactive oxygen species in response to beta-amyloid fibrils. Am. J. Pathol. 160, 101–112 (2002). source

In the paper

“Deficiency in the very-long-chain fatty-acid transporter ABCD1 increased complement activation and synapse loss and aggravated microglial phagocytosis of neurons”

What the sources say

• Not checked yetcites [142] Gong, Y. et al. Microglial dysfunction as a key pathological change in adrenomyeloneuropathy. Ann. Neurol. 82, 813–827 (2017). source

In the paper

“Five progranulin mutations (four missense and one 5′ regulatory variant) are associated with reduction in age at onset and shorter survival after onset of ALS”

What the sources say

• Not checked yetcites [146] Sleegers, K. et al. Progranulin genetic variability contributes to amyotrophic lateral sclerosis. Neurology 71, 253–259 (2008). source

In the paper

“In Aβ-mice, manipulating gut microbiota influences Aβ deposition and alters microglial reactivity and morphology by unknown mechanisms149.”

What the sources say

• Not checked yetcites [149] Minter, M. R. et al. Antibiotic-induced perturbations in gut microbial diversity influences neuro-inflammation and amyloidosis in a murine model of Alzheimer’s disease. Sci. Rep. 6, 30028 (2016). source

In the paper

“Eradication of gut microbiota also alters microglial numbers, size, transcriptomes, and surveillance functions and downregulates host-defense genes147.”

What the sources say

• Not checked yetcites [147] Erny, D. et al. Host microbiota constantly control maturation and function of microglia in the CNS. Nat. Neurosci. 18, 965–977 (2015). source

In the paper

“In a PD model, antibiotic treatment ameliorates PD pathology, whereas oral administration of specific microbial metabolites promotes neuroinflammation and motor symptoms150.”

What the sources say

• Not checked yetcites [150] Sampson, T. R. et al. Gut microbiota regulate motor deficits and neuroinflammation in a model of Parkinson’s disease. Cell 167, 1469–1480.e12 (2016). source