Whether, when and how chronic inflammation increases the risk of developing late-onset Alzheimer's disease

Alzheimer's Research and Therapy

Volumn 4, Issue 3, 2012, Pages

  Eikelenboom, Piet ^a,b,c   Hoozemans, Jeroen J M ^c   Veerhuis, Rob ^c   Van Exel, Eric ^c   Rozemuller, Annemieke J M ^c   Van Gool, Willem A ^b  

^a Valeriuskliniek   (Netherlands)

^b UNIVERSITY OF AMSTERDAM   (Netherlands)

^c VU UNIVERSITY MEDICAL CENTER   (Netherlands)

Author keywords

[No Author keywords available]

Indexed keywords

ACUTE PHASE PROTEIN; ALPHA 1 ANTICHYMOTRYPSIN; ALPHA 2 MACROGLOBULIN; AMYLOID BETA PROTEIN; APOLIPOPROTEIN E; C REACTIVE PROTEIN; CD14 ANTIGEN; CLUSTERIN; COLLAGEN FIBRIL; GAMMA INTERFERON; INTERCELLULAR ADHESION MOLECULE 1; INTERLEUKIN 1BETA; INTERLEUKIN 6; LIPOPOLYSACCHARIDE; NONSTEROID ANTIINFLAMMATORY AGENT; PROTEOHEPARAN SULFATE; SERUM AMYLOID P; TOLL LIKE RECEPTOR; TUMOR NECROSIS FACTOR ALPHA;

ALZHEIMER DISEASE; ASTROCYTE; CHRONIC INFLAMMATION; COGNITIVE DEFECT; COMPLEMENT SYSTEM; CYTOKINE PRODUCTION; DELIRIUM; DEMENTIA; DETERIORATION; GENE LOCUS; GENETIC ASSOCIATION; GENETIC RISK; GLIA CELL; HUMAN; INNATE IMMUNITY; MENTAL DETERIORATION; MICROGLIA; NEUROPATHOLOGY; PRIORITY JOURNAL; PROTEIN BLOOD LEVEL; REVIEW; RISK ASSESSMENT; SENILE PLAQUE; SIGNAL TRANSDUCTION;

EID: 84860811893     PISSN: None     EISSN: 17589193     Source Type: Journal    
DOI: 10.1186/alzrt118     Document Type: Review

References (83)

1. The significance of neuroinflammation in understanding Alzheimer's disease. Eikelenboom P, Veerhuis R, Scheper W, Rozemuller AJM, van Gool WA, Hoozemans JJM, J Neural Transm 2006 113 1685 1695 17036175 (Pubitemid 44657664)
2. Complement activation by -amyloid in Alzheimer's disease. Rogers J, Cooper NR, Webster S, Schulz J, McGeer PL, Styren SD, Civin WH, Brachova L, Bradt B, Lieberburg I, Proc Natl Acad Sci USA 1992 89 10016 10020 1438191
3. Neuroinflamatory processes in Alzheimer's disease. Heneka MT, O'Banion MK, Terwel D, Kummer MP, J Neural Transm 2010 117 919 947 20632195
4. Who fans the flames of Alzheimer's disease brains? Misfolded tau on the crossroad of neurodegenerative and inflammatory pathways. Zilka N, Kazmerova Z, Jadhav S, Neradil P, Madari A, Obetkova D, Bugos O, Novak M, J Neuroinflammation 2012 9 47 22397366
5. Neuroinflammation and regeneration in the early stages of Alzheimer's disease pathology. Hoozemans JJM, Veerhuis R, Rozemuller JM, Eikelenboom P, Int J Dev Neurosci 2006 24 157 165 16384684 (Pubitemid 43294622)
6. In-vivo measurement of microglia in dementia. Cagnin A, Brooks DJ, Kennedy AM, Gunn RN, Myers R, Turkheimer FE, Jones T, Banati RB, Lancet 2001 358 461 467 11513911
7. Microglial activation and amyloid deposition in mild cognitive impairment: a PET study. Okello A, Edison P, Archer HA, Turkheimer FE, Kennedy J, Bullock R, Walker Z, Kennedy A, Fox N, Rossor M, Brooks DJ, Neurology 2009 72 56 62 19122031
8. Immunoglobulins and complement factors in senile plaques. An immunohistoperoxidase study. Eikelenboom P, Stam FC, Acta Neuropathol 1982 57 239 242 6812382 (Pubitemid 12085182)
9. Immunochemical identification of the serine protease inhibitor 1-antichymotrypsin in the brain amyloid deposits of Alzheimer's disease. Abraham CR, Selkoe DJ, Potter H, Cell 1988 52 487 501 3257719 (Pubitemid 18067514)
10. Apoliporotein E immunoreactivity in cerebral amyloid deposits and neurofibrillary tangles in alzheimer's diseaseand kuru plaque amyloid in Creutzfeldt-Jakob disease. Namba Y, Tomonaga M, Kawasaki H, Otomo E, Ikeda K, Brain Res 1991 541 163 166 2029618
11. SP-40,40 is a constituent of Alzheimer's amyloid. Choi-Miura NH, Ihara Y, Fukuchi K, Takeda M, Nakano Y, Tobe T, Tomita M, Acta Neuropathol 1992 83 260 264 1373021
12. Microglial cells around plaques in Alzheimer's disease express leucocyte adhesion molecules of the LFA-1 family. Rozemuller JM, Eikelenboom P, Pals ST, Stam FC, Neurosci Lett 1989 101 288 292 2549464 (Pubitemid 19159426)
13. Interleukin-6 and 2-macroglobulin indicate an acute-phase state in Alzheimer's disease. Bauer J, Strauss S, Schreiter-Gasser U, Ganter U, Schlegel P, Witt I, Yolk B, Berger M, FEBS Lett 1991 285 111 114 1712317
14. Isolation and characterization of amyloid P component from Alzheimer's disease and other types of cerebral amyloidosis. Coria F, Castano E, Prelli F, Larrondo-Lillo M, van Duinen S, Shelanski ML, Frangione B, Lab Invest 1988 58 454 458 2965774
15. The presence of heparin sulfate proteoglycans in the neuritic plaques and congophilic angiopathy in Alzheimer's disease. Snow AD, Mar H, Nochlin D, Kimata K, Kato M, Suzuki S, Hassell J, Wight TN, Am J Pathol 1988 133 456 463 2974240 (Pubitemid 19020577)
16. Amyloid associated proteins in Alzheimer's and prion disease. Veerhuis R, Boshuizen RS, Familian A, Curr Drug Targets CNS Neurol Disord 2005 4 235 248 15975027 (Pubitemid 40754160)
17. Distrubution of -amyloid associated proteins in plaques in Alzheimer's disease and non-demented elderly. Zhan SS, Veerhuis R, Kamphorst W, Eikelenboom P, Neurodegeneration 1994 4 291 297
18. Amyloid- plaque-associated proteins C1q and SAP enhance the A1-42 peptide-induced cytokine production in adult human microglia in vitro. Veerhuis R, van Breemen, Hoozemans JJM, Morbin M, Ouladhadj J, Tagliavini F, Eikelenboom P, Acta Neuropathol 2003 105 135 144 12536224 (Pubitemid 36798799)
19. Loccalization of human serum amyloid P component and heparin sulphate proteoglycan in vitro-formed A fibrils. Holm Nielsen E, Nybo M, Junker K, Toftedal Hansen P, Rasmussen IM, Svehag SE, Scand J Immunol 2000 52 110 112 10931376
20. Cerebral amyloid deposition and diffuse plaques in 'normal' aging. Evidence for presymptomatic and very mild Alzheimer's disease. Morris JC, Storandt M, McKeel DW Jr, Rubin EH, Price JL, Grant EA, Berg L, Neurology 1996 46 707 719 8618671
21. Prominent neurodegeneration and increased plaque formation in complement inhibited Alzheimer's mice. Wyss-Coray T, Yan F, Lin AH, Lambris JD, Alexander JJ, Quigg RJ, Masliah E, Proc Natl Acad Sci USA 2002 99 10837 10842 12119423
22. Complement C3 deficiency leads to accelerated amyloid- plaque deposition and neurodegeneration and modulation of the microglia/macrophage phenotype in amyloid precursor protein transgenic mice. Maier M, Peng Y, Jiang L, Seabrook TJ, Carroll MC, Lemere CA, J Neurosci 2008 28 6333 6341 18562603
23. Lack of apoliprotein E dramatically reduces amyloid -peptide deposition. Bales KR, Verina T, Dodel RC, Du YS, Altstiel L, Bender M, Hyslop P, Johnstone EM, Little SP, Cummins DJ, Ricardo P, Ghetti B, Paul SM, Nat Genet 1997 17 263 264 9354781
24. 1-Antichymotrypsin promotes -sheet amyloid plaque deposition in a transgenic mouse model of Alzheimer's disease. Nilsson LN, Bales KR, DiCarlo G, Gordon MN, Morgan D, Paul SM, Potter H, J Neurosci 2001 21 1444 1451 11222634 (Pubitemid 32182186)
25. Clusterin promotes amyloid plaque formation and it is critical for neuritic toxicity in a mouse model of Alzheimer's disease. DeMattos RB, O'dell MA, Parsadanian M, Taylor JW, Harmony JA, Bales KR, Paul SM, Aronow BJ, Holtzman DM, Proc Natl Acad Sci USA 2002 99 10843 10848 12145324
26. Genome-wide association study identifies variants at CLU and PICALM associated with Alzheimer's disease. Harold D, Abraham R, Hollingworth P, Sims R, Gerrish A, Hamshere ML, Pahwa JS, Moskvina V, Dowzell K, Williams A, Jones N, Thomas C, Stretton A, Morgan AR, Lovestone S, Powell J, Proitsi P, Lupton MK, Brayne C, Rubinsztein DC, Gill M, Lawlor B, Lynch A, Morgan K, Brown KS, Passmore PA, Craig D, McGuinness B, Todd S, Holmes C, et al. Nat Genet 2009 41 1088 1093 19734902
27. Genome-wide association study identifies variants at CLU and CR1 associated with Alzheimer's disease. Lambert JC, Heath S, Even G, Campion D, Sleegers K, Hiltunen M, Combarros O, Zelenika D, Bullido MJ, Tavernier B, Letenneur L, Bettens K, Berr C, Pasquier F, Fievet N, Barberger-Gateau P, Engelborghs S, De Deyn P, Mateo I, Franck A, Helisalmi S, Porcellini E, Hanon O, de Pancorbo MM, Lendon C, Dufouil C, Jaillard C, Leveillard T, Alvarez V, Bosco P, et al. Nat Genet 2009 41 1094 1099 19734903
28. The three new pathways leading to Alzheimer's disease. Morgan K, Neuropathol Appl Neurobiol 2011 37 353 357 21486313
29. Pattern recognition receptors and inflammation. Takeuchi O, Akira S, Cell 2010 140 805 820 20303872
30. The LPS receptor (CD14) links innateimmunity with Alzheimer's disease. Fassbender K, Walter S, Kuhl S, Landmann R, Ishii K, Bertsch T, Stalder AK, Muehlhauser F, Liu Y, Ulmer AJ, Rivest S, Lentschat A, Guulbins E, Jucker M, Staufenbiel M, Brechtel K, Walter J, Multhaup G, Penke BM Adachi Y, Hartmann T, Beyreuther K, Faseb J 2004 18 203 2005 14597556
31. Role of toll-like receptor signalling in A uptake and clearance. Tahara K, Kim HD, Jin JJ, Maxwell JA, Li L, Fukuchi K, Brain 2006 129 3006 3019 16984903 (Pubitemid 44684521)
32. CD14 and toll-like receptors 2 and are required for fibrillar A-stimulated microglial activation. Reed-Geaghan EG, Savage JC, Hise AG, Landreth GE, J Neurosci 2009 29 11982 11992 19776284
33. Induction of toll-like receptor 9 signalling as a ethod for ameliorating Alzheimer's disease-related pathology. Scholtzova H, Kascsak RJ, Bates KA, Boutajangout A, Kerr DJ, Meeker HC, Mehta PD, Spinner DS, Wisniewski T, J Neurosci 2009 29 1846 1854 19211891
34. CD13 ligands promote sterile inflammation through assembly of a Toll-like receptor 4 and 6 dimer. Stewart CR, Stuart LM, Wikinson K, van Gils JM, Deng J, Halle A, Rayner KJ, Boyer L, Zhong R, Frazier WA, Lacy-Hulber A, El Khoury J, Golenbock DT, Moore KJ, Nat Immunol 2010 11 155 161 20037584
35. Role of Toll-like receptor 4 in neuroinflammation in Alzheimer's disease. Walter S, Liu Y, Heine H, Penke B, Hao W, Bode B, Manietta N, Walter J, Schulz-Schaffer W, Kassbender K, Cell Physiol Biochem 2007 20 947 956 17982277 (Pubitemid 350059737)
36. Microglia kill amyloid-1-42 damaged neurons by a CD14-dependent process. Bate C, Veerhuis R, Eikelenboom P, Williams A, NeuroReport 2004 15 1427 1430 15194867 (Pubitemid 38925236)
37. Inflammation in neurodegenerative disease-a double edge sword. Wyss-Coray T, Mucke L, Neuron 2002 35 419 432 12165466 (Pubitemid 34879943)
38. The microglial "activation" continuum: from innate to adaptive responses. Town T, Nikolic V, Tan J, J Neuroinflammation 2005 2 24 16259628
39. Expression profiles for macrophage alternative activation genes in AD and in mouse models of AD. Colton CA, Mott RT, Sharpe H, Van Nostrand WE, Vitek MP, J Neuroinflammation 2006 3 27 17005052
40. Chronic neuroinflammation in rats reproduces components of the neurobiology of Alzheimer's disease. Hauss-Wegrzyniak B, Dobrzanski P, Stoehr JD, Wenk GL, Brain Res 1998 780 294 303 9507169 (Pubitemid 28082916)
41. Heritability estimates of innate immunity: an extended twin study. de Craen AJ, Posthuma D, Remarque EJ, van den Biggelaar AH, Westendorp RGJ, Genes Immun 2005 6 167 170 15674372 (Pubitemid 40439544)
42. Vascular factors and markers of inflammation in offspring with a parental history of late-onset Alzheimer disease. van Exel E, Eikelenboom P, Comijs H, Frolich M, Smit JH, Stek ML, Scheltens P, Eefsting JE, Westendorp RGJ, Arch Gen Psychiat 2009 66 1263 1270 19884614
43. Human cytokine response ex vivo amyloid- is mediated by genetic factors. Posthuma D, Meulenbelt I, de Craen AJM, de Geus EJC, Slagboom PE, Boomsma DI, Westendorp RGJ, Twin Res Hum Genet 2005 8 132 137 15901476 (Pubitemid 40593394)
44. Early inflammation and dementia: a 25-year follow-up of the Honolulu-Asia aging study. Schmidt R, Schmidt H, Curb JD, Masaki K, White LR, Launer LJ, Ann Neurol 2002 52 168 174 12210786 (Pubitemid 34810596)
45. Inflammatory proteins in plasma and the risk of dementia: the Rotterdam study. Engelhart MJ, Geerlings MI, Meijer J, Kilaan A, Ruitenberg A, van Swieten JC, Stijnen T, Hofman A, Witteman JC, Breteler MMB, Arch Neurol 2004 61 668 672 15148142 (Pubitemid 38637682)
46. Serum inflammatory proteins and cognitive decline in older patients. Dik MG, Jonker C, Hack CE, Smit JH, Comijs HC, Eikelenboom P, Neurology 2005 64 1371 1377 15851726 (Pubitemid 40570504)
47. The meatboloc syndrome, inflammation, and the risk of cognitive decline. Yaffe K, Kanaya A, Lindquist K, Simonsick EM, Harris T, Shorr RI, Tylavsky FA, Newman AB, JAMA 2004 292 2237 2242 15536110 (Pubitemid 39473161)
48. Contribution of metabolic syndrome components to cognition in older individuals. Dik MG, Jonker C, Comijs HC, Deeg DJ, Kok A, Yaffe K, Pennix BW, Diabetes Care 2007 30 2655 2660 17563341 (Pubitemid 47547816)
49. Inflammatory markers and the risk of Alzheimer's disease: The Framingham study. Tan ZS, Beiser AS, Vasan RS, Roubenoff R, Dinarello CA, Harris TB, Benjamin EJ, Au R, Kiel DP, Wolf PA, Seshadri S, Neurology 2007 68 1902 1908 17536046 (Pubitemid 46848622)
50. Glial-neuronal interactions in Alzheimer's disease; the potential role of a 'cytokine cycle'in disease progression. Griffin WST, Sheng JG, Royston MC, Mackenzie JE, Graham DI, Roberts GW, Mrak RE, Brain Pathol 1998 8 65 72 9458167 (Pubitemid 28055765)
51. Classification and prediction of clinical Alzheimer's diagnosis based on plasma signaling proteins. Ray S, Britschgi M, Herbert C, Takeda-Uchimura Y, Boxer A, Blennow K, Friedman LF, Galasko DR, Jutel M, Karydas A, Kaye JA, Leszek J, Miller BL, Minthon L, Quinn JF, Rabinovic GD, Robinson WH, Sabbagh MN, So YT, Sparks DL, Tabaton M, Tinklenberg J, Yesavage JA, Tibshirani R, Wyss-Coray T, Nat Med 2007 13 1359 1362 17934472 (Pubitemid 350073592)
52. Immune blood biomarkers of Alzheimer disease patients. Avagyan H, Goldenson B, Tse E, Masoumi A, Porter V, Wiedau-Pazos M, Sayre J, Ong R, Mahanian M, Koo P, Bae S, Micic M, Liu PT, Rosenthal MJ, Fiala M, J Neuroimmunol 2009 210 67 72 19329192
53. The syntax of immune-neuroendocrine communication. Blalock JE, Immunol Today 1994 15 504 511 7802919 (Pubitemid 24327562)
54. From inflammation to sickness and depression: when the immune system subjugates the brain. Dantzer R, O'Connor JC, Freund GG, Johnson RW, Kelly KW, Nat Rev Neurosci 2008 9 46 56 18073775 (Pubitemid 350295688)
55. Alzheimer's disease in 22 twins pairs-13 years follow-up. Hormonal, infectious and traumatic factors. Nee LE, Lippa CF, Dement Geriatr Cogn Disord 1999 10 148 151 10026389 (Pubitemid 29099699)
56. Association between dementia and infectious disease: evidence from a case-control study. Dunn N, Mullee M, Perry VH, Holmes C, Alzheimer Dis Assoc Disord 2005 19 91 94 15942327 (Pubitemid 41073086)
57. Systemic inflammation and disease progression in Alzheimer's disease. Holmes C, Cunningham C, Zotova E, Woolford J, Dean C, Kerr S, Culliford D, Perry VH, Neurology 2009 73 768 774 19738171
58. Periodontol inflammation in relation to cognitive function in an older Danish population. Kamer AR, Morse DE, Holm-Pedersen P, Mortensen EL, Avlund K, J Alzheimers Dis 2012 28 613 624 22045483
59. TNF- and antibodies to periodontal bacteria discriminate between Alzheimer's disease patients and normal subjects. Kamer AR, Craig RG, Pirraglia E, Dasanayaka AP, Norman RG, Boylan RJ, Nehorayoff A, Glodzik L, Brys M, de Leon MJ, J Neuroimmunol 2009 216 92 97 19767111
60. Delirium in the elderly and the risk of postdischarge mortality, institutionalization, and dementia: a meta-analysis. Witlox J, Eurelings LS, de Jonghe JFM, Kalisvaart KJ, Eikelenboom P, van Gool WA, JAMA 2010 304 443 451 20664045
61. Microglia activation in sepsis: a case-control study. Lemstra AW, Groen in't Woud JC, Hoozemans JJ, van Haastert ES, Rozemuller AJ, Eikelenboom P, van Gool WA, J Neuroinflammation 2007 4 4 17224051
62. Neuroinflammation in delirium: a postmortem case-control study. Munster BC, Aronica E, Zwinderman AH, Eikelenboom P, Cunningham C, Rooij SE, Rejuvenation Res 2011 14 615 622 21978081
63. Systemic infection; when cytokines and acetylcholine collide. van Gool WA, van de Beek D, Eikelenboom P, Lancet 2010 375 773 775 20189029
64. Systemic infections and inflammation affect chronic neurodegeneration. Perry VH, Cunningham C, Holmes C, Nat Rev Immunol 2007 7 161 167 17220915 (Pubitemid 46174862)
65. Cytokines and acute phase response in delirium. de Rooij SE, van Munster BC, Korevaar JC, Levi M, J Psychosom Res 2007 62 521 525 17467406 (Pubitemid 46635470)
66. Anesthesia and postoperative delirium in older adults undergoing hip surgery. Slor CJ, de Jonghe JFM, Groot E, van der Ploeg T, van Gool WA, Eikelenboom P, Snoeck M, Schmand B, Kalisvaart KJ, J Am Geriatr Soc 2011 59 1313 1319 21718258
67. Time-course of cytokines during delirium in elderly with hip fractures. van Munster BC, Korevaar JC, Zwinderman AH, Levi M, Wiersinga WJ, de Rooij SE, J Am Geriatr Soc 2008 56 1704 1709 18691278
68. Long-term cognitive outcome of delirium in elderly hip surgery patients. A prospective matched controlled study over two and a half year. Kat MG, Vreeswijk R, de Jonghe JF, van der Ploeg T, van Gool WA, Eikelenboom P, Kalisvaart KJ, Dement Geriatr Cogn Disord 2008 26 1 8 18562793
69. High risk of cognitive and functional decline after postoperative delirium. A three-year prospective study. Bickel H, Gradinger R, Kochs E, Forstl H, Dement Geriatr Cogn Disord 2008 26 26 31 18577850
70. Delirium is an important predictor of incident dementia among elderly hip fracture patient. Krogseth M, Wyller TB, Engedal K, Juliebo V, Dement Geriatr Cogn Disord 2011 31 63 70 21212674
71. Delirium accelerates cognitive decline in Alzheimer disease. Fong TG, Jones RN, Shi P, Maracantonio ER, Yap L, Rudolph JL, Yang FM, Kiely DK, Inouye SK, Neurology 2009 72 1570 1575 19414723
72. Apolipoprotein E inhibits Toll-like receptor (TLR)-3 and TLR-4 mediated macrophage activation through distinct mechanisms. Zhu Y, Kodvawala A, Hui DY, Biochem J 2010 428 47 54 20218969
73. Essential requirement of apolipoprotein J (clusterin) signaling for IB expression and regulation of NF-B activity. Santilli G, Aronow BJ, Sala A, J Biol Chem 2003 278 38214 38219 12882985 (Pubitemid 37221710)
74. Neuroinflammation and disruption in working memory in aged mice after stimulation of the peripheral innate immune system. Chen J, Buchanan JB, Sparkman NL, Godbout JP, Freund GG, Johnson RW, Brain Behav Immun 2008 22 301 311 17951027 (Pubitemid 351172703)
75. Delirium as predictor of long-term cognitive impairment in survivors of critical illness. Girard TD, Jackson JC, Pandharipande PP, Pun BT, Thompson JL, Shintani AK, Gordon SM, Canonico AE, Dittus RS, Bernard GR, Ely EW, Crit Care Med 2010 38 1513 1520 20473145
76. Microglia-neuron interaction in inflammatory and degenerative diseases: role of cholinergic and noradrernegic systems. Carnevale D, de Simone R, Minghetti L, CNS Neurol Disord Drug Targets 2007 6 388 397 18220778 (Pubitemid 351486253)
77. Neurovascular pathways to neurodegeneration in Alzheimer's disease and other disorders. Zlokovic BZ, Nat Rev Neurosci 2011 12 723 738 22048062
78. Neurovascular dysfunction, inflammation and endothelial activation. Implications for the pathogenesis of Alzheimer's disease. Grammas P, J Neuroinfl ammation 2011 8 26
79. Delirium in dementia. Robertsson B, Blennow K, Gottfries CG, Wallin A, Int J Geriatr Psychiatry 1998 13 49 56 9489581 (Pubitemid 28046030)
80. Sustained hippocampal Il-1 overexpression mediates chronic neuroinfklammation and ameliorates Alzheimer plaque pathology. Shaftel SS, Kyrkanides S, Miller JN, Jonson RE, O'Banion MK, J Clin Invest 2007 117 1595 1604 17549256 (Pubitemid 46871344)
81. Non-steroidal anti-inflammatory drugs and Alzheimer's disease: the epidemiological evidence. Szekely CA, Zandi PP, CNS Neurol Disord Drug Targets 2010 9 132 139 20205647
82. Cyclooxygenase-1 and -2 in the different stages of Alzheimer's disease pathology. Hoozemans JJM, Rozemuller JM, van Haastert ES, Veerhuis R, Eikelenboom P, Curr Pharm Des 2008 14 1419 1427 18537664 (Pubitemid 351982549)
83. Minocycline does not affect amyloid- phagocytosis. Familian A, Eikelenboom P, Veerhuis R, Neurosci Lett 2007 416 87 91 17317005