Early molecular and synaptic dysfunctions in the prodromal stages of Alzheimer’s disease: focus on TNF-α and IL-1β

Papers of special note have been highlighted as: ▪ of interest ▪▪ of considerable interest

Bibliography

• 1  Hardy J. A hundred years of Alzheimer’s disease research. Neuron52(1),3–13 (2006).
  Medline CASGoogle Scholar
• 2  Terry RD, Masliah E, Salmon DP et al. Physical basis of cognitive alterations in Alzheimer’s disease: synapse loss is the major correlate of cognitive impairment. Ann. Neurol.30(4),572–580 (1991).
  Medline CASGoogle Scholar
• 3  Akiyama H, Barger S, Barnum S et al. Inflammation and Alzheimer’s disease. Neurobiol. Aging21(3),383–421 (2000).
  Medline CASGoogle Scholar
• 4  Wood JA, Wood PL, Ryan R et al. Cytokine indices in Alzheimer’s temporal cortex: no changes in mature IL-1β or IL-1RA but increases in the associated acute phase proteins IL-6, α 2-macroglobulin and C-reactive protein. Brain Res.629(2),245–252 (1993).
  Medline CASGoogle Scholar
• 5  Heneka MT, O’Banion MK. Inflammatory processes in Alzheimer’s disease. J. Neuroimmunol.184(1–2),69–91 (2007).
  Medline CASGoogle Scholar
• 6  Lee YJ, Han SB, Nam SY, Oh KW, Hong JT. Inflammation and Alzheimer’s disease. Arch. Pharm. Res.33(10),1539–1556 (2010).
  Medline CASGoogle Scholar
• 7  McGeer EG, McGeer PL. Neuroinflammation in Alzheimer’s disease and mild cognitive impairmen: a field in its infancy. J. Alzheimers Dis.19(1),355–361 (2010).
  MedlineGoogle Scholar
• 8  Eikelenboom P, Veerhuis R. The importance of inflammatory mechanisms for the development of Alzheimer’s disease. Exp. Gerontol.34(3),453–461 (1999).
  Medline CASGoogle Scholar
• 9  Hollingworth P, Harold D, Jones L, Owen MJ, Williams J. Alzheimer’s disease genetics: current knowledge and future challenges. Int. J. Geriatr. Psychiat.26(8),793–802 (2011).
  MedlineGoogle Scholar
• 10  Hollingworth P, Harold D, Sims R et al. Common variants at ABCA7, MS4A6A/MS4A4E, EPHA1, CD33 and CD2AP are associated with Alzheimer’s disease. Nat. Genet.43(5),429–435 (2011).
  Medline CASGoogle Scholar
• 11  Ferretti MT, Bruno MA, Ducatenzeiler A, Klein WL, Cuello AC. Intracellular Aβ-oligomers and early inflammation in a model of Alzheimer’s disease. Neurobiol. Aging doi: 10.1016/j.neurobiolaging.2011.01.007 (2011) (Epub ahead of print).▪ Provides evidence of early inflammatory markers and microglial activation in a preplaque mouse model of Alzheimer’s disease (AD).
  MedlineGoogle Scholar
• 12  Yirmiya R, Goshen I. Immune modulation of learning, memory, neural plasticity and neurogenesis. Brain Behav. Immun.25(2),181–213 (2011).
  Medline CASGoogle Scholar
• 13  Clark IA, Alleva LM, Vissel B. The roles of TNF in brain dysfunction and disease. Pharmacol. Ther.128(3),519–548 (2010).
  Medline CASGoogle Scholar
• 14  Mcafoose J, Baune BT. Evidence for a cytokine model of cognitive function. Neurosci. Biobehav. Rev.33(3),355–366 (2009).
  Medline CASGoogle Scholar
• 15  Malenka RC, Nicoll RA. Long-term potentiation – a decade of progress? Science285(5435),1870–1874 (1999).
  Medline CASGoogle Scholar
• 16  Stellwagen D, Malenka RC. Synaptic scaling mediated by glial TNF-α. Nature440(7087),1054–1059 (2006).▪ Determines the role of TNF-α in synaptic scaling.
  Medline CASGoogle Scholar
• 17  Ogoshi F, Yin HZ, Kuppumbatti Y, Song B, Amindari S, Weiss JH. Tumor necrosis-factor-α (TNF-α) induces rapid insertion of Ca²⁺-permeable α-amino-3-hydroxyl-5-methyl-4-isoxazole-propionate (AMPA)/kainate (Ca-A/K) channels in a subset of hippocampal pyramidal neurons. Exp. Neurol.193(2),384–393 (2005).
  Medline CASGoogle Scholar
• 18  Viviani B, Gardoni F, Marinovich M. Cytokines and neuronal ion channels in health and disease. Int. Rev. Neurobiol.82,247–263 (2007).
  Medline CASGoogle Scholar
• 19  Park KM, Bowers WJ. Tumor necrosis factor-α mediated signaling in neuronal homeostasis and dysfunction. Cell. Signal.22(7),977–983 (2010).
  Medline CASGoogle Scholar
• 20  Stellwagen D, Beattie EC, Seo JY, Malenka RC. Differential regulation of AMPA receptor and GABA receptor trafficking by tumor necrosis factor-α. J. Neurosci.25(12),3219–3228 (2005).
  Medline CASGoogle Scholar
• 21  Rainey-Smith SR, Andersson DA, Williams RJ, Rattray M. Tumour necrosis factor α induces rapid reduction in AMPA receptor-mediated calcium entry in motor neurones by increasing cell surface expression of the GluR2 subunit: relevance to neurodegeneration. J. Neurochem.113(3),692–703 (2010).
  Medline CASGoogle Scholar
• 22  Albensi BC, Mattson MP. Evidence for the involvement of TNF and NF-κB in hippocampal synaptic plasticity. Synapse35(2),151–159 (2000).
  Medline CASGoogle Scholar
• 23  Gerber J, Bottcher T, Hahn M, Siemer A, Bunkowski S, Nau R. Increased mortality and spatial memory deficits in TNF-α-deficient mice in ceftriaxone-treated experimental pneumococcal meningitis. Neurobiol. Dis.16(1),133–138 (2004).
  Medline CASGoogle Scholar
• 24  Fogal B, Hewett SJ. Interleukin-1β: a bridge between inflammation and excitotoxicity? J. Neurochem.106(1),1–23 (2008).
  Medline CASGoogle Scholar
• 25  Avital A, Goshen I, Kamsler A et al. Impaired interleukin-1 signaling is associated with deficits in hippocampal memory processes and neural plasticity. Hippocampus13(7),826–834 (2003).
  Medline CASGoogle Scholar
• 26  Goshen I, Kreisel T, Ounallah-Saad H et al. A dual role for interleukin-1 in hippocampal-dependent memory processes. Psychoneuroendocrinology32(8–10),1106–1115 (2007).
  Medline CASGoogle Scholar
• 27  Yirmiya R, Winocur G, Goshen I. Brain interleukin-1 is involved in spatial memory and passive avoidance conditioning. Neurobiol. Learn. Mem.78(2),379–389 (2002).
  Medline CASGoogle Scholar
• 28  Viviani B, Boraso M. Cytokines and neuronal channels: a molecular basis for age-related decline of neuronal function? Exp. Gerontol.46(2–3),199–206 (2011).▪▪ Recent review addressing the mechanisms of cytokine interaction with neuronal ion channels to regulate neuronal excitability, synaptic plasticity and injury response in normal and pathological aging.
  Medline CASGoogle Scholar
• 29  Leonoudakis D, Zhao P, Beattie EC. Rapid tumor necrosis factor α-induced exocytosis of glutamate receptor 2-lacking AMPA receptors to extrasynaptic plasma membrane potentiates excitotoxicity. J. Neurosci.28(9),2119–2130 (2008).
  Medline CASGoogle Scholar
• 30  Santello M, Bezzi P, Volterra A. TNFα controls glutamatergic gliotransmission in the hippocampal dentate gyrus. Neuron69(5),988–1001 (2011).
  Medline CASGoogle Scholar
• 31  Li G, Bauer S, Nowak M et al. Cytokines and epilepsy. Seizure20(3),249–256 (2011).
  MedlineGoogle Scholar
• 32  Lai AY, Swayze RD, EL-Husseini A, Song C. Interleukin-1β modulates AMPA receptor expression and phosphorylation in hippocampal neurons. J. Neuroimmunol.175(1–2),97–106 (2006).
  Medline CASGoogle Scholar
• 33  Zhang R, Sun L, Hayashi Y et al. Acute p38-mediated inhibition of NMDA-induced outward currents in hippocampal CA1 neurons by interleukin-1β. Neurobiol. Dis.38(1),68–77 (2010).
  MedlineGoogle Scholar
• 34  Zhang R, Yamada J, Hayashi Y, Wu Z, Koyama S, Nakanishi H. Inhibition of NMDA-induced outward currents by interleukin-1β in hippocampal neurons. Biochem. Biophys. Res. Commun.372(4),816–820 (2008).
  Medline CASGoogle Scholar
• 35  Butler MP, O’Connor JJ, Moynagh PN. Dissection of tumor-necrosis factor-α inhibition of long-term potentiation (LTP) reveals a p38 mitogen-activated protein kinase-dependent mechanism which maps to early- but not late-phase LTP. Neuroscience124(2),319–326 (2004).
  Medline CASGoogle Scholar
• 36  Cumiskey D, Butler MP, Moynagh PN, O’Connor JJ. Evidence for a role for the group I metabotropic glutamate receptor in the inhibitory effect of tumor necrosis factor-α on long-term potentiation. Brain Res.1136(1),13–19 (2007).
  Medline CASGoogle Scholar
• 37  Tancredi V, D’Arcangelo G, Grassi F et al. Tumor necrosis factor alters synaptic transmission in rat hippocampal slices. Neurosci. Lett.146(2),176–178 (1992).
  Medline CASGoogle Scholar
• 38  Katsuki H, Nakai S, Hirai Y, Akaji K, Kiso Y, Satoh M. Interleukin-1β inhibits long-term potentiation in the CA3 region of mouse hippocampal slices. Eur. J. Pharmacol.181(3),323–326 (1990).
  Medline CASGoogle Scholar
• 39  Bellinger FP, Madamba S, Siggins GR. Interleukin 1β inhibits synaptic strength and long-term potentiation in the rat CA1 hippocampus. Brain Res.628(1–2),227–234 (1993).
  Medline CASGoogle Scholar
• 40  Cunningham AJ, Murray CA, O’Neill LA, Lynch MA, O’Connor JJ. Interleukin-1β (IL-1β) and tumour necrosis factor (TNF) inhibit long-term potentiation in the rat dentate gyrus in vitro. Neurosci. Lett.203(1),17–20 (1996).
  Medline CASGoogle Scholar
• 41  Hellstrom IC, Danik M, Luheshi GN, Williams S. Chronic LPS exposure produces changes in intrinsic membrane properties and a sustained IL-β-dependent increase in GABAergic inhibition in hippocampal CA1 pyramidal neurons. Hippocampus15(5),656–664 (2005).
  Medline CASGoogle Scholar
• 42  Coan EJ, Irving AJ, Collingridge GL. Low-frequency activation of the NMDA receptor system can prevent the induction of LTP. Neurosci. Lett.105(1–2),205–210 (1989).
  Medline CASGoogle Scholar
• 43  Vereker E, O’Donnell E, Lynch MA. The inhibitory effect of interleukin-1β on long-term potentiation is coupled with increased activity of stress-activated protein kinases. J. Neurosci.20(18),6811–6819 (2000).
  Medline CASGoogle Scholar
• 44  Barry CE, Nolan Y, Clarke RM, Lynch A, Lynch MA. Activation of c-Jun-N-terminal kinase is critical in mediating lipopolysaccharide-induced changes in the rat hippocampus. J. Neurochem.93(1),221–231 (2005).
  Medline CASGoogle Scholar
• 45  Hu NW, Ondrejcak T, Rowan MJ. Glutamate receptors in preclinical research on Alzheimer’s disease: update on recent advances. Pharmacol. Biochem. Behav. doi: 10.1016/j.pbb.2011.04.013 (2011) (Epub ahead of print).▪ Detailed review summarizing recent studies on the earliest glutamatergic alterations in preclinical AD.
  MedlineGoogle Scholar
• 46  Jolas T, Zhang XS, Zhang Q et al. Long-term potentiation is increased in the CA1 area of the hippocampus of APP^swe/ind CRND8 mice. Neurobiol. Dis.11(3),394–409 (2002).
  Medline CASGoogle Scholar
• 47  Schmid AW, Lynch MA, Herron CE. The effects of IL-1 receptor antagonist on β amyloid mediated depression of LTP in the rat CA1 in vivo. Hippocampus19(7),670–676 (2009).
  Medline CASGoogle Scholar
• 48  Wang Q, Wu J, Rowan MJ, Anwyl R. β-amyloid inhibition of long-term potentiation is mediated via tumor necrosis factor. Eur. J. Neurosci.22(11),2827–2832 (2005).▪▪ One of the few studies directly addressing and implicating TNF-α in long-term potentiation inhibition within the context of AD.
  MedlineGoogle Scholar
• 49  Hu NW, Klyubin I, Anwyl R, Rowan MJ. GluN2B subunit-containing NMDA receptor antagonists prevent Aβ-mediated synaptic plasticity disruption in vivo. Proc. Natl Acad. Sci. USA106(48),20504–20509 (2009).
  Medline CASGoogle Scholar
• 50  Noebels J. A perfect storm: converging paths of epilepsy and Alzheimer’s dementia intersect in the hippocampal formation. Epilepsia52(Suppl. 1.),39–46 (2011).
  MedlineGoogle Scholar
• 51  Palop JJ, Mucke L. Epilepsy and cognitive impairments in Alzheimer disease. Arch. Neurol.66(4),435–440 (2009).
  MedlineGoogle Scholar
• 52  Del Vecchio RA, Gold LH, Novick SJ, Wong G, Hyde LA. Increased seizure threshold and severity in young transgenic CRND8 mice. Neurosci. Lett.367(2),164–167 (2004).
  Medline CASGoogle Scholar
• 53  Palop JJ, Chin J, Roberson ED et al. Aberrant excitatory neuronal activity and compensatory remodeling of inhibitory hippocampal circuits in mouse models of Alzheimer’s disease. Neuron55(5),697–711 (2007).
  Medline CASGoogle Scholar
• 54  Gleichmann M, Mattson MP. Alzheimer’s disease and neuronal network activity. Neuromol. Med.12(1),44–47 (2010).
  Medline CASGoogle Scholar
• 55  Kumar-Singh S, Dewachter I, Moechars D et al. Behavioral disturbances without amyloid deposits in mice overexpressing human amyloid precursor protein with Flemish (A692G) or Dutch (E693Q) mutation. Neurobiol. Dis.7(1),9–22 (2000).
  Medline CASGoogle Scholar
• 56  Lalonde R, Dumont M, Staufenbiel M, Strazielle C. Neurobehavioral characterization of APP23 transgenic mice with the SHIRPA primary screen. Behav. Brain Res.157(1),91–98 (2005).
  Medline CASGoogle Scholar
• 57  Minkeviciene R, Rheims S, Dobszay MB et al. Amyloid β-induced neuronal hyperexcitability triggers progressive epilepsy. J. Neurosci.29(11),3453–3462 (2009).
  Medline CASGoogle Scholar
• 58  Ondrejcak T, Klyubin I, Hu NW, Barry AE, Cullen WK, Rowan MJ. Alzheimer’s disease amyloid β-protein and synaptic function. Neuromol. Med.12(1),13–26 (2010).
  Medline CASGoogle Scholar
• 59  Moult PR, Correa SA, Collingridge GL, Fitzjohn SM, Bashir ZI. Co-activation of p38 mitogen-activated protein kinase and protein tyrosine phosphatase underlies metabotropic glutamate receptor-dependent long-term depression. J. Physiol.586(10),2499–2510 (2008).
  Medline CASGoogle Scholar
• 60  Selkoe DJ. Soluble oligomers of the amyloid β-protein impair synaptic plasticity and behavior. Behav. Brain Res.192(1),106–113 (2008).
  Medline CASGoogle Scholar
• 61  Moretti DV, Pievani M, Geroldi C et al. EEG markers discriminate among different subgroup of patients with mild cognitive impairment. Am. J. Alzheimers Dis. Other Demen.25(1),58–73 (2010).
  Medline CASGoogle Scholar
• 62  Czigler B, Csikos D, Hidasi Z et al. Quantitative EEG in early Alzheimer’s disease patients – power spectrum and complexity features. Int. J. Psychophysiol.68(1),75–80 (2008).
  MedlineGoogle Scholar
• 63  Van Der Hiele K, Vein AA, Van Der Welle A et al. EEG and MRI correlates of mild cognitive impairment and Alzheimer’s disease. Neurobiol. Aging28(9),1322–1329 (2007).
  Medline CASGoogle Scholar
• 64  Van Deursen JA, Vuurman EF, Verhey FR, Van Kranen-Mastenbroek VH, Riedel WJ. Increased EEG γ band activity in Alzheimer’s disease and mild cognitive impairment. J. Neural Transm.115(9),1301–1311 (2008).
  Medline CASGoogle Scholar
• 65  Herrmann CS, Demiralp T. Human EEG γ oscillations in neuropsychiatric disorders. Clin. Neurophysiol.116(12),2719–2733 (2005).
  Medline CASGoogle Scholar
• 66  Goutagny R, Jackson G, Chabot J-G et al. Very early alterations of hippocampal network oscillations in transgenic TgCRND8 mouse model of Alzheimer’s disease. Presented AT: Society for Neuroscience 2010. San Diego, CA, USA, 13–17 November 2010.
  Google Scholar
• 67  Jelic V, Johansson SE, Almkvist O et al. Quantitative electroencephalography in mild cognitive impairment: longitudinal changes and possible prediction of Alzheimer’s disease. Neurobiol. Aging21(4),533–540 (2000).
  Medline CASGoogle Scholar
• 68  Vialatte FB, Dauwels J, Maurice M, Musha T, Cichocki A. Improving the specificity of EEG for diagnosing Alzheimer’s disease. Int. J. Alzheimers Dis.2011,259069 (2011).
  MedlineGoogle Scholar
• 69  Palop JJ, Mucke L. Synaptic depression and aberrant excitatory network activity in Alzheimer’s disease: two faces of the same coin? Neuromol. Med.12(1),48–55 (2010).
  Medline CASGoogle Scholar
• 70  Colom LV. Septal networks: relevance to θ rhythm, epilepsy and Alzheimer’s disease. J. Neurochem.96(3),609–623 (2006).
  Medline CASGoogle Scholar
• 71  Colom LV, Garcia-Hernandez A, Castaneda MT, Perez-Cordova MG, Garrido-Sanabria ER. Septo–hippocampal networks in chronically epileptic rats: potential antiepileptic effects of θ rhythm generation. J. Neurophysiol.95(6),3645–3653 (2006).
  MedlineGoogle Scholar
• 72  Licastro F, Chiappelli M, Ruscica M, Carnelli V, Corsi MM. Altered cytokine and acute phase response protein levels in the blood of children with Downs syndrome: relationship with dementia of Alzheimer’s type. Int. J. Immunopathol. Pharmacol.18(1),165–172 (2005).
  Medline CASGoogle Scholar
• 73  Tan ZS, Beiser AS, Vasan RS et al. Inflammatory markers and the risk of Alzheimer disease: the Framingham study. Neurology68(22),1902–1908 (2007).
  Medline CASGoogle Scholar
• 74  Breitner JC, Baker LD, Montine TJ et al. Extended results of the Alzheimer’s disease anti-inflammatory prevention trial. Alzheimers Dement.7(4),402–411 (2011).
  MedlineGoogle Scholar
• 75  Heneka MT, Sastre M, Dumitrescu-Ozimek L et al. Focal glial activation coincides with increased BACE1 activation and precedes amyloid plaque deposition in APP^V717I transgenic mice. J. Neuroinflammation2,22 (2005).
  MedlineGoogle Scholar
• 76  Janelsins MC, Mastrangelo MA, Oddo S, Laferla FM, Federoff HJ, Bowers WJ. Early correlation of microglial activation with enhanced tumor necrosis factor-α and monocyte chemoattractant protein-1 expression specifically within the entorhinal cortex of triple transgenic Alzheimer’s disease mice. J. Neuroinflammation2,23 (2005).
  MedlineGoogle Scholar
• 77  Ma K, Mount HT, McLaurin J. Region-specific distribution of β-amyloid peptide and cytokine expression in TgCRND8 mice. Neurosci. Lett.492(1),5–10 (2011).
  Medline CASGoogle Scholar
• 78  Cavanagh C, Krantic S, Goutagny R et al. Increased hippocampal sensitivity to epileptiform activity in one month old TgCRND8 mice: correlation with the level of bCTF expression. Presented AT: 10th International Conference on Alzheimer’s and Parkinson’s Disease. Barcelona, Spain, 9–13 March 2011.
  Google Scholar
• 79  Yoshiyama Y. [Neurodegeneration and inflammation: analysis of a FTDP-17 model mouse]. Rinsho Shinkeigaku48(11),910–912 (2008).
  MedlineGoogle Scholar
• 80  Heurtaux T, Michelucci A, Losciuto S et al. Microglial activation depends on β-amyloid conformation: role of the formylpeptide receptor 2. J. Neurochem.114(2),576–586 (2010).
  Medline CASGoogle Scholar
• 81  Chang KA, Suh YH. Pathophysiological roles of amyloidogenic carboxy-terminal fragments of the β-amyloid precursor protein in Alzheimer’s disease. J. Pharmacol. Sci.97(4),461–471 (2005).
  Medline CASGoogle Scholar
• 82  Blasko I, Veerhuis R, Stampfer-Kountchev M, Saurwein-Teissl M, Eikelenboom P, Grubeck-Loebenstein B. Costimulatory effects of interferon-γ and interleukin-1β or tumor necrosis factor α on the synthesis of Aβ_1–40 and Aβ_1–42 by human astrocytes. Neurobiol. Dis.7(6 Pt B),682–689 (2000).
  Medline CASGoogle Scholar
• 83  Yamamoto M, Kiyota T, Horiba M et al. Interferon-γ and tumor necrosis factor-α regulate amyloid-β plaque deposition and β-secretase expression in Swedish mutant APP transgenic mice. Am. J. Pathol.170(2),680–692 (2007).
  Medline CASGoogle Scholar
• 84  Buchhave P, Zetterberg H, Blennow K, Minthon L, Janciauskiene S, Hansson O. Soluble TNF receptors are associated with Aβ metabolism and conversion to dementia in subjects with mild cognitive impairment. Neurobiol. Aging31(11),1877–1884 (2010).
  Medline CASGoogle Scholar
• 85  Liao YF, Wang BJ, Cheng HT, Kuo LH, Wolfe MS. Tumor necrosis factor-α, interleukin-1β, and interferon-γ stimulate γ-secretase-mediated cleavage of amyloid precursor protein through a JNK-dependent MAPK pathway. J. Biol. Chem.279(47),49523–49532 (2004).▪ Demonstrates how certain cytokines can contribute to increased AD pathology by increasing the production of amyloid-β. Higher levels of amyloid-β would lead to increased release of cytokines, creating a vicious feed-forward cycle.
  Medline CASGoogle Scholar
• 86  Lahiri DK, Chen D, Vivien D, Ge YW, Greig NH, Rogers JT. Role of cytokines in the gene expression of amyloid β-protein precursor: identification of a 5´-UTR-binding nuclear factor and its implications in Alzheimer’s disease. J. Alzheimers Dis.5(2),81–90 (2003).
  Medline CASGoogle Scholar
• 87  Jacobsen JS, Wu CC, Redwine JM et al. Early-onset behavioral and synaptic deficits in a mouse model of Alzheimer’s disease. Proc. Natl Acad. Sci. USA103(13),5161–5166 (2006).
  Medline CASGoogle Scholar
• 88  Rammes G, Hasenjager A, Sroka-Saidi K, Deussing JM, Parsons CG. Therapeutic significance of NR2B-containing NMDA receptors and mGluR5 metabotropic glutamate receptors in mediating the synaptotoxic effects of β-amyloid oligomers on long-term potentiation (LTP) in murine hippocampal slices. Neuropharmacology60(6),982–990 (2011).
  Medline CASGoogle Scholar
• 89  Wang Q, Walsh DM, Rowan MJ, Selkoe DJ, Anwyl R. Block of long-term potentiation by naturally secreted and synthetic amyloid β-peptide in hippocampal slices is mediated via activation of the kinases c-Jun N-terminal kinase, cyclin-dependent kinase 5, and p38 mitogen-activated protein kinase as well as metabotropic glutamate receptor type 5. J. Neurosci.24(13),3370–3378 (2004).
  Medline CASGoogle Scholar
• 90  Mcalpine FE, Lee JK, Harms AS et al. Inhibition of soluble TNF signaling in a mouse model of Alzheimer’s disease prevents pre-plaque amyloid-associated neuropathology. Neurobiol. Dis.34(1),163–177 (2009).▪▪ Demonstrates the involvement of TNF signaling in the development of early AD pathology.
  Medline CASGoogle Scholar
• 91  Shi JQ, Shen W, Chen J et al. Anti-TNF-α reduces amyloid plaques and tau phosphorylation and induces CD11c-positive dendritic-like cell in the APP/PS1 transgenic mouse brains. Brain Res.1368,239–247 (2010).
  MedlineGoogle Scholar
• 92  Chavant F, Deguil J, Pain S et al. Imipramine, in part through tumor necrosis factor α inhibition, prevents cognitive decline and β-amyloid accumulation in a mouse model of Alzheimer’s disease. J. Pharmacol. Exp. Ther.332(2),505–514 (2010).
  Medline CASGoogle Scholar
• 93  Morihara T, Teter B, Yang F et al. Ibuprofen suppresses interleukin-1β induction of pro-amyloidogenic α₁-antichymotrypsin to ameliorate β-amyloid (Aβ) pathology in Alzheimer’s models. Neuropsychopharmacology30(6),1111–1120 (2005).
  Medline CASGoogle Scholar
• 94  Giuliani F, Vernay A, Leuba G, Schenk F. Decreased behavioral impairments in an Alzheimer mice model by interfering with TNF-α metabolism. Brain Res. Bull.80(4–5),302–308 (2009).
  Medline CASGoogle Scholar
• 95  Schroeder T. Hematopoietic stem cell heterogeneity: subtypes, not unpredictable behavior. Cell Stem Cell6(3),203–207 (2010).
  Medline CASGoogle Scholar
• 96  Kettenmann H, Hanisch UK, Noda M, Verkhratsky A. Physiology of microglia. Physiol. Rev.91(2),461–553 (2011).
  Medline CASGoogle Scholar
• 97  Mucke L, Sanchez P, Yu G-Q, Palop J, Cisse M, Verret L. Mechanisms and treatment of neuronal dysfunction in models of Alzheimer’s disease. Presented AT: International Conference on Alzheimer’s Disease 2011. Paris, France, 16–21 July 2011.
  Google Scholar
• 98  Frankola KA, Greig NH, Luo W, Tweedie D. Targeting TNF-α to elucidate and ameliorate neuroinflammation in neurodegenerative diseases. CNS Neurol. Disord. Drug Targets10(3),391–403 (2011).
  Medline CASGoogle Scholar
• 99  Tobinick EL, Gross H. Rapid cognitive improvement in Alzheimer’s disease following perispinal etanercept administration. J. Neuroinflammation5,2 (2008).
  MedlineGoogle Scholar
• 100  Tobinick E, Gross H, Weinberger A, Cohen H. TNF-α modulation for treatment of Alzheimer’s disease: a 6-month pilot study. Med. Gen. Med.8(2),25 (2006).
  Google Scholar
• 101  Griffin WS. Perispinal etanercept: potential as an Alzheimer therapeutic. J. Neuroinflammation5,3 (2008).
  MedlineGoogle Scholar
• 102  Munoz L, Ralay Ranaivo H, Roy SM et al. A novel p38 α MAPK inhibitor suppresses brain proinflammatory cytokine up-regulation and attenuates synaptic dysfunction and behavioral deficits in an Alzheimer’s disease mouse model. J. Neuroinflammation4,21 (2007).
  MedlineGoogle Scholar
• 103  Tang W, Lu Y, Tian QY et al. The growth factor progranulin binds to TNF receptors and is therapeutic against inflammatory arthritis in mice. Science332(6028),478–484 (2011).
  Medline CASGoogle Scholar
• 104  Bossu P, Salani F, Alberici A et al. Loss of function mutations in the progranulin gene are related to pro-inflammatory cytokine dysregulation in frontotemporal lobar degeneration patients. J. Neuroinflammation8,65 (2011).
  Medline CASGoogle Scholar
• 105  Baker M, Mackenzie IR, Pickering-Brown SM et al. Mutations in progranulin cause tau-negative frontotemporal dementia linked to chromosome 17. Nature442(7105),916–919 (2006).
  Medline CASGoogle Scholar
• 106  Wee Yong V. Inflammation in neurological disorders: a help or a hindrance? Neuroscientist16(4),408–420 (2010).
  Medline CASGoogle Scholar
• 107  Weldon DT, Rogers SD, Ghilardi JR et al. Fibrillar β-amyloid induces microglial phagocytosis, expression of inducible nitric oxide synthase, and loss of a select population of neurons in the rat CNS in vivo. J. Neurosci.18(6),2161–2173 (1998).
  Medline CASGoogle Scholar
• 108  Zalevsky J, Secher T, Ezhevsky SA et al. Dominant-negative inhibitors of soluble TNF attenuate experimental arthritis without suppressing innate immunity to infection. J. Immunol.179(3),1872–1883 (2007).
  Medline CASGoogle Scholar
• 109  Scheinfeld N. A comprehensive review and evaluation of the side effects of the tumor necrosis factor α blockers etanercept, infliximab and adalimumab. J. Dermatolog. Treat.15(5),280–294 (2004).
  Medline CASGoogle Scholar
• 110  Montgomery SL, Bowers WJ. Tumor necrosis factor-α and the roles it plays in homeostatic and degenerative processes within the central nervous system. J. Neuroimmune Pharmacol. doi: 10.1007/s11481-011-9287-2 (2011) (Epub ahead of print).
  MedlineGoogle Scholar
• 111  Tobinick E. Perispinal etanercept produces rapid improvement in primary progressive aphasia: identification of a novel, rapidly reversible TNF-mediated pathophysiologic mechanism. Medscape J. Med.10(6),135 (2008).
  MedlineGoogle Scholar
• 112  Golde TE, Schneider LS, Koo EH. Anti-αβ therapeutics in Alzheimer’s disease: the need for a paradigm shift. Neuron69(2),203–213 (2011).
  Medline CASGoogle Scholar