A link between nerve growth factor metabolic deregulation and amyloid-β-driven inflammation in down syndrome

CNS and Neurological Disorders - Drug Targets

Volumn 15, Issue 4, 2016, Pages 434-447

  Iulita, Maria Florencia ^a   Caraci, Filippo ^b,c   Cuello, Augusto Claudio ^a  

^a MCGILL UNIVERSITY   (Canada)

^b UNIVERSITY OF CATANIA   (Italy)

^c OASI RESEARCH INSTITUTE IRCCS   (Italy)

Author keywords

Alzheimer s disease; Cholinergic neurons; Down syndrome; Inflammation; Metallo proteases; Nerve growth factor; Nerve growth factor metabolism

Indexed keywords

4 AMINOBUTYRIC ACID; AMYLOID BETA PROTEIN; CHOLINE ACETYLTRANSFERASE; INTERLEUKIN 1BETA; NERVE GROWTH FACTOR; NEUROTROPHIN; VESICULAR ACETYLCHOLINE TRANSPORTER;

ALZHEIMER DISEASE; ARTICLE; CHROMOSOME 21; CHROMOSOME TRANSLOCATION; COGNITIVE DEFECT; DEMENTIA; DOWN SYNDROME; ENZYME LINKED IMMUNOSORBENT ASSAY; GENE EXPRESSION; INFLAMMATION; LIFE EXPECTANCY; NERVE DEGENERATION; NUCLEAR MAGNETIC RESONANCE IMAGING; PHENOTYPE; PROTEIN EXPRESSION; TRISOMY; BRAIN; CHOLINERGIC NERVE CELL; HUMAN; METABOLISM; PATHOLOGY; SIGNAL TRANSDUCTION;

ALZHEIMER DISEASE; AMYLOID BETA-PEPTIDES; BRAIN; CHOLINERGIC NEURONS; DOWN SYNDROME; HUMANS; NERVE GROWTH FACTOR; SIGNAL TRANSDUCTION;

EID: 84964042560     PISSN: 18715273     EISSN: 19963181     Source Type: Journal    
DOI: 10.2174/1871527315666160321104916     Document Type: Article

References (184)

1. Hardy J. The amyloid hypothesis for Alzheimer’s disease: a critical reappraisal. J Neurochem 2009; 110: 1129-34.
2. Querfurth HW, LaFerla FM. Alzheimer’s disease. N Engl J Med 2010; 362: 329-44.
3. Reitz C, Brayne C, Mayeux R. Epidemiology of Alzheimer disease. Nat Rev Neurol 2011; 7: 137-52.
4. Cummings JL, Khachaturian ZS. Definitions and Diagnostic Criteria. In: Gauthier S, Ed. Clinical Diagnosis and Management of Alzheimer’s Disease. London NW1 0AE: The Livery House, 2001; 2nd revised ed: pp. 3-13.
5. Ballard C, Day S, Sharp S, Wing G, Sorensen S. Neuropsychiatric symptoms in dementia: importance and treatment considerations. Int Rev Psychiatry 2008; 20: 396-404.
6. Hardy J, Allsop D. Amyloid deposition as the central event in the aetiology of Alzheimer’s disease. Trends Pharmacol Sci 1991; 12: 383-8.
7. Walsh DM, Selkoe DJ. A beta oligomers - a decade of discovery. J Neurochem 2007; 101: 1172-84.
8. Haass C. Initiation and propagation of neurodegeneration. Nat Med 2010; 16: 1201-4.
9. Cleary JP, Walsh DM, Hofmeister JJ, et al. Natural oligomers of the amyloid-beta protein specifically disrupt cognitive function. Nat Neurosci 2005; 8: 79-84.
10. Deshpande A, Mina E, Glabe C, Busciglio J. Different conformations of amyloid beta induce neurotoxicity by distinct mechanisms in human cortical neurons. J Neurosci 2006; 26: 6011-8.
11. Lambert MP, Barlow AK, Chromy BA, et al. Diffusible, nonfibrillar ligands derived from Abeta1-42 are potent central nervous system neurotoxins. Proc Natl Acad Sci USA 1998; 95: 6448-53.
12. Shankar GM, Li S, Mehta TH, et al. Amyloid-beta protein dimers isolated directly from Alzheimer’s brains impair synaptic plasticity and memory. Nat Med 2008; 14: 837-42.
13. Walsh DM, Klyubin I, Fadeeva JV, et al. Naturally secreted oligomers of amyloid beta protein potently inhibit hippocampal long-term potentiation in vivo. Nature 2002; 416: 535-9.
14. Lue LF, Kuo YM, Roher AE, et al. Soluble amyloid beta peptide concentration as a predictor of synaptic change in Alzheimer’s disease. Am J Pathol 1999; 155: 853-62.
15. Caraci F, Copani A, Nicoletti F, Drago F. Depression and Alzheimer’s disease: neurobiological links and common pharmacological targets. Eur J Pharmacol 2010; 626: 64-71.
16. Mann DM. The pathological association between Down syndrome and Alzheimer disease. Mech Ageing Dev 1988; 43: 99-136.
17. Mann DM, Jones D, Prinja D, Purkiss MS. The prevalence of amyloid (A4) protein deposits within the cerebral and cerebellar cortex in Down’s syndrome and Alzheimer’s disease. Acta Neuropathol 1990; 80: 318-27.
18. Wisniewski KE, Wisniewski HM, Wen GY. Occurrence of neuropathological changes and dementia of Alzheimer’s disease in Down’s syndrome. Ann Neurol 1985; 17: 278-82.
19. Zigman WB, Devenny DA, Krinsky-McHale SJ, et al. Alzheimer’s Disease in Adults with Down Syndrome. Int Rev Res Ment Retard 2008; 36: 103-45.
20. Mann DM, Esiri MM. The pattern of acquisition of plaques and tangles in the brains of patients under 50 years of age with Down’s syndrome. J Neurol Sci 1989; 89: 169-79.
21. Zigman WB, Schupf N, Sersen E, Silverman W. Prevalence of dementia in adults with and without Down syndrome. Am J Ment Retard 1996; 100: 403-12.
22. Lai F, Williams RS. A prospective study of Alzheimer disease in Down syndrome. Arch Neurol 1989; 46: 849-53.
23. Head E, Powell D, Gold BT, Schmitt FA. Alzheimer’s Disease in Down Syndrome. Eur J Neurodegener Dis 2012; 1: 353-64.
24. Picker JD, Walsh CA. New innovations: therapeutic opportunities for intellectual disabilities. Ann Neurol 2013; 74: 382-90.
25. Bruno MA, Leon WC, Fragoso G, Mushynski WE, Almazan G, Cuello AC. Amyloid beta-induced nerve growth factor dysmetabolism in Alzheimer disease. J Neuropathol Exp Neurol 2009; 68: 857-69.
26. Iulita MF, Do Carmo S, Ower AK, et al. Nerve growth factor metabolic dysfunction in Down’s syndrome brains. Brain 2014; 137: 860-72.
27. Carter CO, Hamerton JL, Polani PE, Gunalp A, Weller SD. Chromosome translocation as a cause of familial mongolism. Lancet 1960; 2: 678-80.
28. Clarke CM, Ford CE, Edwards JH, Smallpeice V. 21 Trisomy/Normal Mosaicism in an Intelligent Child with Some Mongoloid Characters. Lancet 1963; 2: 1229.
29. Gardiner K, Herault Y, Lott IT, Antonarakis SE, Reeves RH, Dierssen M. Down syndrome: from understanding the neurobiology to therapy. J Neurosci 2010; 30: 14943-5.
30. Teipel SJ, Alexander GE, Schapiro MB, Moller HJ, Rapoport SI, Hampel H. Age-related cortical grey matter reductions in nondemented Down’s syndrome adults determined by MRI with voxelbased morphometry. Brain 2004; 127: 811-24.
31. Raz N, Torres IJ, Briggs SD, et al. Selective neuroanatomic abnormalities in Down’s syndrome and their cognitive correlates: evidence from MRI morphometry. Neurology 1995; 45: 356-66.
32. Kesslak JP, Nagata SF, Lott I, Nalcioglu O. Magnetic resonance imaging analysis of age-related changes in the brains of individuals with Down’s syndrome. Neurology 1994; 44: 1039-45.
33. Roth GM, Sun B, Greensite FS, Lott IT, Dietrich RB. Premature aging in persons with Down syndrome: MR findings. AJNR Am J Neuroradiol 1996; 17: 1283-9.
34. Golden JA, Hyman BT. Development of the superior temporal neocortex is anomalous in trisomy 21. J Neuropathol Exp Neurol 1994; 53: 513-20.
35. Ross MH, Galaburda AM, Kemper TL. Down’s syndrome: is there a decreased population of neurons? Neurology 1984; 34: 909-16.
36. Rissman RA, Mobley WC. Implications for treatment: GABAA receptors in aging, Down syndrome and Alzheimer’s disease. J Neurochem 2011; 117: 613-22.
37. Lott IT, Dierssen M. Cognitive deficits and associated neurological complications in individuals with Down’s syndrome. Lancet Neurol 2010; 9: 623-33.
38. Roizen NJ, Patterson D. Down’s syndrome. Lancet 2003; 361: 1281-9.
39. O’Caoimh R, Clune Y, Molloy DW. Screening for Alzheimer’s Disease in Downs Syndrome. J Alzheimers Dis Parkinson 2013; 2013: S7.
40. Lott IT, Dierssen M. Cognitive deficits and associated neurological complications in individuals with Down’s syndrome. Lancet Neurol 2010; 9: 623-33.
41. Chapman RS, Hesketh LJ. Behavioral phenotype of individuals with Down syndrome. Ment Retard Dev Disabil Res Rev 2000; 6: 84-95.
42. Glasson EJ, Sullivan SG, Hussain R, Petterson BA, Montgomery PD, Bittles AH. The changing survival profile of people with Down’s syndrome: implications for genetic counselling. Clin Genet 2002; 62: 390-3.
43. Glasson EJ, Dye DE, Bittles AH. The triple challenges associated with age-related comorbidities in Down syndrome. J Intellect Disabil Res 2014; 58: 393-8.
44. Head E, Silverman W, Patterson D, Lott IT. Aging and down syndrome. Curr Gerontol Geriatr Res 2012; 2012: 412536.
45. Zigman W, Silverman W, Wisniewski HM. Aging and Alzheimer’s disease in Down syndrome: Clinical and pathological changes. Mental Retard Devel Disabil Res Rev 1996; 2: 73-9.
46. Bittles AH, Bower C, Hussain R, Glasson EJ. The four ages of Down syndrome. Eur J Public Health 2007; 17: 221-5.
47. Zigman WB, Lott IT. Alzheimer’s disease in Down syndrome: neurobiology and risk. Ment Retard Dev Disabil Res Rev 2007; 13: 237-46.
48. Oyama F, Cairns NJ, Shimada H, Oyama R, Titani K, Ihara Y. Down’s syndrome: up-regulation of beta-amyloid protein precursor and tau mRNAs and their defective coordination. J Neurochem 1994; 62: 1062-6.
49. Teller JK, Russo C, DeBusk LM, et al. Presence of soluble amyloid beta-peptide precedes amyloid plaque formation in Down’s syndrome. Nat Med 1996; 2: 93-5.
50. Cataldo AM, Peterhoff CM, Troncoso JC, Gomez-Isla T, Hyman BT, Nixon RA. Endocytic pathway abnormalities precede amyloid beta deposition in sporadic Alzheimer’s disease and Down syndrome: differential effects of APOE genotype and presenilin mutations. Am J Pathol 2000; 157: 277-86.
51. Grbovic OM, Mathews PM, Jiang Y, et al. Rab5-stimulated upregulation of the endocytic pathway increases intracellular betacleaved amyloid precursor protein carboxyl-terminal fragment levels and Abeta production. J Biol Chem 2003; 278: 31261-8.
52. Nistor M, Don M, Parekh M, et al. Alpha- and beta-secretase activity as a function of age and beta-amyloid in Down syndrome and normal brain. Neurobiol Aging 2007; 28: 1493-506.
53. Lemere CA, Blusztajn JK, Yamaguchi H, Wisniewski T, Saido TC, Selkoe DJ. Sequence of deposition of heterogeneous amyloid betapeptides and APO E in Down syndrome: implications for initial events in amyloid plaque formation. Neurobiol Dis 1996; 3: 16-32.
54. Gyure KA, Durham R, Stewart WF, Smialek JE, Troncoso JC. Intraneuronal abeta-amyloid precedes development of amyloid plaques in Down syndrome. Arch Pathol Lab Med 2001; 125: 489-92.
55. Mori C, Spooner ET, Wisniewsk KE, et al. Intraneuronal Abeta42 accumulation in Down syndrome brain. Amyloid 2002; 9: 88-102.
56. Leverenz JB, Raskind MA. Early amyloid deposition in the medial temporal lobe of young Down syndrome patients: a regional quantitative analysis. Exp Neurol 1998; 150: 296-304.
57. Handen BL, Cohen AD, Channamalappa U, et al. Imaging brain amyloid in nondemented young adults with Down syndrome using Pittsburgh compound B. Alzheimers Dement 2012; 8: 496-501.
58. Azizeh BY, Head E, Ibrahim MA, et al. Molecular dating of senile plaques in the brains of individuals with Down syndrome and in aged dogs. Exp Neurol 2000; 163: 111-22.
59. Lott IT. Neurological phenotypes for Down syndrome across the life span. Prog Brain Res 2012; 197: 101-21.
60. Ball SL, Holland AJ, Treppner P, Watson PC, Huppert FA. Executive dysfunction and its association with personality and behaviour changes in the development of Alzheimer’s disease in adults with Down syndrome and mild to moderate learning disabilities. Br J Clin Psychol 2008; 47: 1-29.
61. Cooper SA, Prasher VP. Maladaptive behaviours and symptoms of dementia in adults with Down’s syndrome compared with adults with intellectual disability of other aetiologies. J Intellect Disabil Res 1998; 42(Pt 4): 293-300.
62. Burt DB, Loveland KA, Lewis KR. Depression and the onset of dementia in adults with mental retardation. Am J Ment Retard 1992; 96: 502-11.
63. Tyrrell J, Cosgrave M, McCarron M, et al. Dementia in people with Down’s syndrome. Int J Geriatr Psychiatry 2001; 16: 1168-74.
64. Dierssen M, Herault Y, Estivill X. Aneuploidy: from a physiological mechanism of variance to Down syndrome. Physiol Rev 2009; 89: 887-920.
65. Schupf N, Sergievsky GH. Genetic and host factors for dementia in Down’s syndrome. Br J Psychiatry 2002; 180: 405-10.
66. Bennett DA, Arnold SE, Valenzuela MJ, Brayne C, Schneider JA. Cognitive and social lifestyle: links with neuropathology and cognition in late life. Acta Neuropathol 2014; 127: 137-50.
67. Prasher VP, Farrer MJ, Kessling AM, et al. Molecular mapping of Alzheimer-type dementia in Down’s syndrome. Ann Neurol 1998; 43: 380-3.
68. Jack CR, Jr., Knopman DS, Jagust WJ, et al. Tracking pathophysiological processes in Alzheimer’s disease: an updated hypothetical model of dynamic biomarkers. Lancet Neurol 2013; 12: 207-16.
69. Villemagne VL, Burnham S, Bourgeat P, et al. Amyloid beta deposition, neurodegeneration, and cognitive decline in sporadic Alzheimer’s disease: a prospective cohort study. Lancet Neurol 2013; 12: 357-67.
70. Sperling RA, Karlawish J, Johnson KA. Preclinical Alzheimer disease-the challenges ahead. Nat Rev Neurol 2013; 9: 54-8.
71. van Oijen M, Hofman A, Soares HD, Koudstaal PJ, Breteler MM. Plasma Abeta(1-40) and Abeta(1-42) and the risk of dementia: a prospective case-cohort study. Lancet Neurol 2006; 5: 655-60.
72. Sundelof J, Giedraitis V, Irizarry MC, et al. Plasma beta amyloid and the risk of Alzheimer disease and dementia in elderly men: a prospective, population-based cohort study. Arch Neurol 2008; 65: 256-63.
73. Lambert JC, Schraen-Maschke S, Richard F, et al. Association of plasma amyloid beta with risk of dementia: the prospective Three-City Study. Neurology 2009; 73: 847-53.
74. Mayeux R, Schupf N. Blood-based biomarkers for Alzheimer’s disease: plasma Abeta40 and Abeta42, and genetic variants. Neurobiol Aging 2011; 32 Suppl 1: S10-9.
75. Head E, Doran E, Nistor M, et al. Plasma amyloid-beta as a function of age, level of intellectual disability, and presence of dementia in Down syndrome. J Alzheimers Dis 2011; 23: 399-409.
76. Schupf N, Patel B, Silverman W, et al. Elevated plasma amyloid beta-peptide 1-42 and onset of dementia in adults with Down syndrome. Neurosci Lett 2001; 301: 199-203.
77. Mehta PD, Mehta SP, Fedor B, Patrick BA, Emmerling M, Dalton AJ. Plasma amyloid beta protein 1-42 levels are increased in old Down Syndrome but not in young Down Syndrome. Neurosci Lett 2003; 342: 155-8.
78. Mehta PD, Capone G, Jewell A, Freedland RL. Increased amyloid beta protein levels in children and adolescents with Down syndrome. J Neurol Sci 2007; 254: 22-7.
79. Tokuda T, Fukushima T, Ikeda S, et al. Plasma levels of amyloid beta proteins Abeta1-40 and Abeta1-42(43) are elevated in Down’s syndrome. Ann Neurol 1997; 41: 271-3.
80. Schupf N, Patel B, Pang D, et al. Elevated plasma beta-amyloid peptide Abeta(42) levels, incident dementia, and mortality in Down syndrome. Arch Neurol 2007; 64: 1007-13.
81. Schupf N, Zigman WB, Tang MX, et al. Change in plasma Ass peptides and onset of dementia in adults with Down syndrome. Neurology 2010; 75: 1639-44.
82. Coppus AM, Schuur M, Vergeer J, et al. Plasma beta amyloid and the risk of Alzheimer’s disease in Down syndrome. Neurobiol Aging 2012; 33: 1988-94.
83. Joachim CL, Mori H, Selkoe DJ. Amyloid beta-protein deposition in tissues other than brain in Alzheimer’s disease. Nature 1989; 341: 226-30.
84. Pallister C, Jung SS, Shaw I, Nalbantoglu J, Gauthier S, Cashman NR. Lymphocyte content of amyloid precursor protein is increased in Down’s syndrome and aging. Neurobiol Aging 1997; 18: 97-103.
85. Mufson EJ, Counts SE, Perez SE, Ginsberg SD. Cholinergic system during the progression of Alzheimer’s disease: therapeutic implications. Expert Rev Neurother 2008; 8: 1703-18.
86. Etienne P, Robitaille Y, Wood P, Gauthier S, Nair NP, Quirion R. Nucleus basalis neuronal loss, neuritic plaques and choline acetyltransferase activity in advanced Alzheimer’s disease. Neuroscience 1986; 19: 1279-91.
87. Pearson RC, Sofroniew MV, Cuello AC, et al. Persistence of cholinergic neurons in the basal nucleus in a brain with senile dementia of the Alzheimer’s type demonstrated by immunohistochemical staining for choline acetyltransferase. Brain Res 1983; 289: 375-9.
88. Mufson EJ, Bothwell M, Kordower JH. Loss of nerve growth factor receptor-containing neurons in Alzheimer’s disease: a quantitative analysis across subregions of the basal forebrain. Exp Neurol 1989; 105: 221-32.
89. Mufson EJ, Ma SY, Cochran EJ, et al. Loss of nucleus basalis neurons containing trkA immunoreactivity in individuals with mild cognitive impairment and early Alzheimer’s disease. J Comp Neurol 2000; 427: 19-30.
90. Vogels OJ, Broere CA, ter Laak HJ, ten Donkelaar HJ, Nieuwenhuys R, Schulte BP. Cell loss and shrinkage in the nucleus basalis Meynert complex in Alzheimer’s disease. Neurobiol Aging 1990; 11: 3-13.
91. Whitehouse PJ, Price DL, Struble RG, Clark AW, Coyle JT, Delon MR. Alzheimer’s disease and senile dementia: loss of neurons in the basal forebrain. Science 1982; 215: 1237-9.
92. Cuello AC, Sofroniew MV. The anatomy of the CNS cholinergic neurons. Trends Neurosci 1984; 7: 74-8.
93. Drachman DA, Leavitt J. Human memory and the cholinergic system. A relationship to aging? Arch Neurol 1974; 30: 113-21.
94. Bartus RT, Dean RL, 3rd, Beer B, Lippa AS. The cholinergic hypothesis of geriatric memory dysfunction. Science 1982; 217: 408-14.
95. Cuello AC. Effects of trophic factors on the CNS cholinergic phenotype. Prog Brain Res 1996; 109: 347-58.
96. Cuello AC. Nerve Growth Factor. In: Stolerman IP, Ed.; Encyclopedia of Psychopharmacology. Springer-Verlag Berlin Heidelberg, 2013; pp. 823-30.
97. Gibbs RB, Pfaff DW. In situ hybridization detection of trkA mRNA in brain: distribution, colocalization with p75NGFR and up-regulation by nerve growth factor. J Comp Neurol 1994; 341: 324-39.
98. Holtzman DM, Li Y, Parada LF, et al. p140trk mRNA marks NGFresponsive forebrain neurons: evidence that trk gene expression is induced by NGF. Neuron 1992; 9: 465-78.
99. Figueiredo BC, Skup M, Bedard AM, Tetzlaff W, Cuello AC. Differential expression of p140trk, p75NGFR and growthassociated phosphoprotein-43 genes in nucleus basalis magnocellularis, thalamus and adjacent cortex following neocortical infarction and nerve growth factor treatment. Neuroscience 1995; 68: 29-45.
100. Venero JL, Knusel B, Beck KD, Hefti F. Expression of neurotrophin and trk receptor genes in adult rats with fimbria transections: effect of intraventricular nerve growth factor and brain-derived neurotrophic factor administration. Neuroscience 1994; 59: 797-815.
101. Pongrac JL, Rylett RJ. NGF-induction of the expression of ChAT mRNA in PC12 cells and primary cultures of embryonic rat basal forebrain. Brain Res Mol Brain Res 1998; 62: 25-34.
102. Auld DS, Mennicken F, Quirion R. Nerve growth factor rapidly induces prolonged acetylcholine release from cultured basal forebrain neurons: differentiation between neuromodulatory and neurotrophic influences. J Neurosci 2001; 21: 3375-82.
103. Oosawa H, Fujii T, Kawashima K. Nerve growth factor increases the synthesis and release of acetylcholine and the expression of vesicular acetylcholine transporter in primary cultured rat embryonic septal cells. J Neurosci Res 1999; 57: 381-7.
104. Mobley WC, Rutkowski JL, Tennekoon GI, Buchanan K, Johnston MV. Choline acetyltransferase activity in striatum of neonatal rats increased by nerve growth factor. Science 1985; 229: 284-7.
105. Debeir T, Saragovi HU, Cuello AC. A nerve growth factor mimetic TrkA antagonist causes withdrawal of cortical cholinergic boutons in the adult rat. Proc Natl Acad Sci USA 1999; 96: 4067-72.
106. Fahnestock M, Scott SA, Jette N, Weingartner JA, Crutcher KA. Nerve growth factor mRNA and protein levels measured in the same tissue from normal and Alzheimer’s disease parietal cortex. Brain Res Mol Brain Res 1996; 42: 175-8.
107. Goedert M, Fine A, Hunt SP, Ullrich A. Nerve growth factor mRNA in peripheral and central rat tissues and in the human central nervous system: lesion effects in the rat brain and levels in Alzheimer’s disease. Brain Res 1986; 387: 85-92.
108. Fahnestock M, Michalski B, Xu B, Coughlin MD. The precursor pro-nerve growth factor is the predominant form of nerve growth factor in brain and is increased in Alzheimer’s disease. Mol Cell Neurosci 2001; 18: 210-20.
109. Pedraza CE, Podlesniy P, Vidal N, et al. Pro-NGF isolated from the human brain affected by Alzheimer’s disease induces neuronal apoptosis mediated by p75NTR. Am J Pathol 2005; 166: 533-43.
110. Bruno MA, Cuello AC. Activity-dependent release of precursor nerve growth factor, conversion to mature nerve growth factor, and its degradation by a protease cascade. Proc Natl Acad Sci USA 2006; 103: 6735-40.
111. Blochl A, Thoenen H. Characterization of nerve growth factor (NGF) release from hippocampal neurons: evidence for a constitutive and an unconventional sodium-dependent regulated pathway. Eur J Neurosci 1995; 7: 1220-8.
112. Blochl A, Thoenen H. Localization of cellular storage compartments and sites of constitutive and activity-dependent release of nerve growth factor (NGF) in primary cultures of hippocampal neurons. Mol Cell Neurosci 1996; 7: 173-90.
113. Yepes M, Lawrence DA. Tissue-type plasminogen activator and neuroserpin: a well-balanced act in the nervous system? Trends Cardiovasc Med 2004; 14: 173-80.
114. Miranda E, Lomas DA. Neuroserpin: a serpin to think about. Cell Mol Life Sci 2006; 63: 709-22.
115. Seiler M, Schwab ME. Specific retrograde transport of nerve growth factor (NGF) from neocortex to nucleus basalis in the rat. Brain Res 1984; 300: 33-9.
116. Howe CL, Valletta JS, Rusnak AS, Mobley WC. NGF signaling from clathrin-coated vesicles: evidence that signaling endosomes serve as a platform for the Ras-MAPK pathway. Neuron 2001; 32: 801-14.
117. Yong VW, Power C, Forsyth P, Edwards DR. Metalloproteinases in biology and pathology of the nervous system. Nat Rev Neurosci 2001; 2: 502-11.
118. Allard S, Leon WC, Pakavathkumar P, Bruno MA, Ribeiro-da-Silva A, Cuello AC. Impact of the NGF maturation and degradation pathway on the cortical cholinergic system phenotype. J Neurosci 2012; 32: 2002-12.
119. Cuello AC, Bruno MA, Allard S, Leon W, Iulita MF. Cholinergic involvement in Alzheimer’s disease. A link with NGF maturation and degradation. J Mol Neurosci 2010; 40: 230-5.
120. Bruno MA, Mufson EJ, Wuu J, Cuello AC. Increased matrix metalloproteinase 9 activity in mild cognitive impairment. Journal of neuropathology and experimental neurology 2009; 68: 1309-18.
121. Peng S, Wuu J, Mufson EJ, Fahnestock M. Increased proNGF levels in subjects with mild cognitive impairment and mild Alzheimer disease. J Neuropathol Exp Neurol 2004; 63: 641-9.
122. Petersen RC. Mild cognitive impairment as a diagnostic entity. J Intern Med 2004; 256: 183-94.
123. Markesbery WR, Schmitt FA, Kryscio RJ, Davis DG, Smith CD, Wekstein DR. Neuropathologic substrate of mild cognitive impairment. Arch Neurol 2006; 63: 38-46.
124. Bowen DM, Smith CB, White P, Davison AN. Neurotransmitterrelated enzymes and indices of hypoxia in senile dementia and other abiotrophies. Brain 1976; 99: 459-96.
125. Davies P, Maloney AJ. Selective loss of central cholinergic neurons in Alzheimer’s disease. Lancet 1976; 2: 1403.
126. Jette N, Cole MS, Fahnestock M. NGF mRNA is not decreased in frontal cortex from Alzheimer’s disease patients. Brain Res Mol Brain Res 1994; 25: 242-50.
127. Yates CM, Simpson J, Maloney AF, Gordon A, Reid AH. Alzheimer-like cholinergic deficiency in Down syndrome. Lancet 1980; 2: 979.
128. Casanova MF, Walker LC, Whitehouse PJ, Price DL. Abnormalities of the nucleus basalis in Down’s syndrome. Ann Neurol 1985; 18: 310-3.
129. Mann DM, Yates PO, Marcyniuk B, Ravindra CR. Loss of neurones from cortical and subcortical areas in Down’s syndrome patients at middle age. Quantitative comparisons with younger Down’s patients and patients with Alzheimer’s disease. J Neurol Sci 1987; 80: 79-89.
130. Bruno MA, Leon WC, Fragoso G, Mushynski WE, Almazan G, Cuello AC. Amyloid beta-induced nerve growth factor dysmetabolism in Alzheimer disease. J Neuropathol Exp Neurol 2009; 68: 857-69.
131. Holtzman DM, Santucci D, Kilbridge J, et al. Developmental abnormalities and age-related neurodegeneration in a mouse model of Down syndrome. Proc Natl Acad Sci USA 1996; 93: 13333-8.
132. Cooper JD, Salehi A, Delcroix JD, et al. Failed retrograde transport of NGF in a mouse model of Down’s syndrome: reversal of cholinergic neurodegenerative phenotypes following NGF infusion. Proc Natl Acad Sci USA 2001; 98: 10439-44.
133. Hunter CL, Isacson O, Nelson M, et al. Regional alterations in amyloid precursor protein and nerve growth factor across age in a mouse model of Down’s syndrome. Neurosci Res 2003; 45: 437-45.
134. Salehi A, Delcroix JD, Belichenko PV, et al. Increased App expression in a mouse model of Down’s syndrome disrupts NGF transport and causes cholinergic neuron degeneration. Neuron 2006; 51: 29-42.
135. Bateman RJ, Xiong C, Benzinger TL, et al. Clinical and biomarker changes in dominantly inherited Alzheimer’s disease. N Engl J Med 2012; 367: 795-804.
136. Sperling RA, Johnson KA, Doraiswamy PM, et al. Amyloid deposition detected with florbetapir F 18 ((18)F-AV-45) is related to lower episodic memory performance in clinically normal older individuals. Neurobiol Aging 2013; 34: 822-31.
137. Deb S, Gottschall PE. Increased production of matrix metalloproteinases in enriched astrocyte and mixed hippocampal cultures treated with beta-amyloid peptides. J Neurochem 1996; 66: 1641-7.
138. Deb S, Wenjun Zhang J, Gottschall PE. Beta-amyloid induces the production of active, matrix-degrading proteases in cultured rat astrocytes. Brain Res 2003; 970: 205-13.
139. Gottschall PE, Yu X, Bing B. Increased production of gelatinase B (matrix metalloproteinase-9) and interleukin-6 by activated rat microglia in culture. J Neurosci Res 1995; 42: 335-42.
140. Gottschall PE, Yu X. Cytokines regulate gelatinase A, B (matrix metalloproteinase 2 and 9) activity in cultured rat astrocytes. J Neurochem 1995; 64: 1513-20.
141. Gu Z, Kaul M, Yan B, et al. S-nitrosylation of matrix metalloproteinases: signaling pathway to neuronal cell death. Science 2002; 297: 1186-90.
142. Pagenstecher A, Stalder AK, Kincaid CL, Shapiro SD, Campbell IL. Differential expression of matrix metalloproteinase and tissue inhibitor of matrix metalloproteinase genes in the mouse central nervous system in normal and inflammatory states. Am J Pathol 1998; 152: 729-41.
143. Bugno M, Witek B, Bereta J, Bereta M, Edwards DR, Kordula T. Reprogramming of TIMP-1 and TIMP-3 expression profiles in brain microvascular endothelial cells and astrocytes in response to proinflammatory cytokines. FEBS Lett 1999; 448: 9-14.
144. Ferretti MT, Partridge V, Leon WC, et al. Transgenic mice as a model of pre-clinical Alzheimer’s disease. Curr Alzheimer Res 2011; 8: 4-23.
145. Ferretti MT, Bruno MA, Ducatenzeiler A, Klein WL, Cuello AC. Intracellular Abeta-oligomers and early inflammation in a model of Alzheimer’s disease. Neurobiol Aging 2012; 33: 1329-42.
146. Hanzel CE, Pichet-Binette A, Pimentel LS, et al. Neuronal driven pre-plaque inflammation in a transgenic rat model of Alzheimer’s disease. Neurobiol Aging 2014; 35: 2249-62.
147. Do Carmo S, Cuello AC. Modeling Alzheimer’s disease in transgenic rats. Mol Neurodegener 2013; 8: 37.
148. Iulita MF, Allard S, Richter L, et al. Intracellular Abeta pathology and early cognitive impairments in a transgenic rat overexpressing human amyloid precursor protein: a multidimensional study. Acta Neuropathol Commun 2014; 2: 61.
149. Leon WC, Canneva F, Partridge V, et al. A novel transgenic rat model with a full Alzheimer’s-like amyloid pathology displays preplaque intracellular amyloid-beta-associated cognitive impairment. J Alzheimers Dis 2010; 20: 113-26.
150. Simard AR, Soulet D, Gowing G, Julien JP, Rivest S. Bone marrow-derived microglia play a critical role in restricting senile plaque formation in Alzheimer’s disease. Neuron 2006; 49: 489-502.
151. Griciuc A, Serrano-Pozo A, Parrado AR, et al. Alzheimer’s disease risk gene CD33 inhibits microglial uptake of amyloid beta. Neuron 2013; 78: 631-43.
152. Guerreiro R, Wojtas A, Bras J, et al. TREM2 variants in Alzheimer’s disease. N Engl J Med 2013; 368: 117-27.
153. Ferretti MT, Cuello AC. Does a pro-inflammatory process precede Alzheimer’s disease and mild cognitive impairment? Curr Alzheimer Res 2011; 8: 164-74.
154. McGeer PL, McGeer E, Rogers J, Sibley J. Anti-inflammatory drugs and Alzheimer disease. Lancet 1990; 335: 1037.
155. McGeer PL, Rogers J. Anti-inflammatory agents as a therapeutic approach to Alzheimer’s disease. Neurology 1992; 42: 447-9.
156. Stewart WF, Kawas C, Corrada M, Metter EJ. Risk of Alzheimer’s disease and duration of NSAID use. Neurology 1997; 48: 626-32.
157. Parachikova A, Agadjanyan MG, Cribbs DH, et al. Inflammatory changes parallel the early stages of Alzheimer disease. Neurobiol Aging 2007; 28: 1821-33.
158. Ray S, Britschgi M, Herbert C, et al. Classification and prediction of clinical Alzheimer’s diagnosis based on plasma signaling proteins. Nat Med 2007; 13: 1359-62.
159. Galimberti D, Fenoglio C, Lovati C, et al. Serum MCP-1 levels are increased in mild cognitive impairment and mild Alzheimer’s disease. Neurobiol Aging 2006; 27: 1763-8.
160. Doecke JD, Laws SM, Faux NG, et al. Blood-based protein biomarkers for diagnosis of Alzheimer disease. Arch Neurol 2012; 69: 1318-25.
161. Schuitemaker A, Dik MG, Veerhuis R, et al. Inflammatory markers in AD, MCI patients with different biomarker profiles. Neurobiol Aging 2009; 30: 1885-9.
162. Okello A, Edison P, Archer HA, et al. Microglial activation and amyloid deposition in mild cognitive impairment: a PET study. Neurology 2009; 72: 56-62.
163. Griffin WS, Stanley LC, Ling C, et al. Brain interleukin 1 and S-100 immunoreactivity are elevated in Down syndrome and Alzheimer disease. Proc Natl Acad Sci USA 1989; 86: 7611-5.
164. Eikelenboom P, Rozemuller JM, van Muiswinkel FL. Inflammation and Alzheimer’s disease: relationships between pathogenic mechanisms and clinical expression. Exp Neurol 1998; 154: 89-98.
165. McGeer PL, Itagaki S, Tago H, McGeer EG. Reactive microglia in patients with senile dementia of the Alzheimer type are positive for the histocompatibility glycoprotein HLA-DR. Neurosci Lett 1987; 79: 195-200.
166. Wilcock DM. Neuroinflammation in the aging down syndrome brain; lessons from Alzheimer’s disease. Curr Gerontol Geriatr Res 2012; 2012: 170276.
167. Wilcock DM, Griffin WS. Down’s syndrome, neuroinflammation, and Alzheimer neuropathogenesis. J Neuroinflammation 2013; 10: 84.
168. Ferretti MT, Allard S, Partridge V, Ducatenzeiler A, Cuello AC. Minocycline corrects early, pre-plaque neuroinflammation and inhibits BACE-1 in a transgenic model of Alzheimer’s disease-like amyloid pathology. J Neuroinflammation 2012; 9: 62.
169. Hunter CL, Bachman D, Granholm AC. Minocycline prevents cholinergic loss in a mouse model of Down’s syndrome. Ann Neurol 2004; 56: 675-88.
170. Jaturapatporn D, Isaac MG, McCleery J, Tabet N. Aspirin, steroidal and non-steroidal anti-inflammatory drugs for the treatment of Alzheimer’s disease. Cochrane Database Syst Rev 2012; 2: CD006378.
171. Breitner JC, Baker LD, Montine TJ, et al. Extended results of the Alzheimer’s disease anti-inflammatory prevention trial. Alzheimers Dement 2011; 7: 402-11.
172. Perry EK, Gibson PH, Blessed G, Perry RH, Tomlinson BE. Neurotransmitter enzyme abnormalities in senile dementia. Choline acetyltransferase and glutamic acid decarboxylase activities in necropsy brain tissue. J Neurol Sci 1977; 34: 247-65.
173. DeKosky ST, Scheff SW, Markesbery WR. Laminar organization of cholinergic circuits in human frontal cortex in Alzheimer’s disease and aging. Neurology 1985; 35: 1425-31.
174. Mesulam MM, Geula C. Acetylcholinesterase-rich pyramidal neurons in the human neocortex and hippocampus: absence at birth, development during the life span, and dissolution in Alzheimer’s disease. Ann Neurol 1988; 24: 765-73.
175. Geula C, Mesulam MM. Cortical cholinergic fibers in aging and Alzheimer’s disease: a morphometric study. Neuroscience 1989; 33: 469-81.
176. Eriksdotter Jonhagen M, Nordberg A, Amberla K, et al. Intracerebroventricular infusion of nerve growth factor in three patients with Alzheimer’s disease. Dement Geriatr Cogn Disord 1998; 9: 246-57.
177. Tuszynski MH, Thal L, Pay M, et al. A phase 1 clinical trial of nerve growth factor gene therapy for Alzheimer disease. Nat Med 2005; 11: 551-5.
178. Rafii MS, Baumann TL, Bakay RA, et al. A phase1 study of stereotactic gene delivery of AAV2-NGF for Alzheimer’s disease. Alzheimers Dement 2014; 10: 571-81.
179. Eriksdotter-Jonhagen M, Linderoth B, Lind G, et al. Encapsulated cell biodelivery of nerve growth factor to the Basal forebrain in patients with Alzheimer’s disease. Dement Geriatr Cogn Disord 2012; 33: 18-28.
180. Ferreira D, Westman E, Eyjolfsdottir H, et al. Brain changes in Alzheimer’s disease patients with implanted encapsulated cells releasing nerve growth factor. J Alzheimers Dis 2015; 43: 1059-72.
181. Bruno MA, Mufson EJ, Wuu J, Cuello AC. Increased matrix metalloproteinase 9 activity in mild cognitive impairment. J Neuropathol Exp Neurol 2009; 68: 1309-18.
182. Backstrom JR, Miller CA, Tokes ZA. Characterization of neutral proteinases from Alzheimer-affected and control brain specimens: identification of calcium-dependent metalloproteinases from the hippocampus. J Neurochem 1992; 58: 983-92.
183. Peng S, Wuu J, Mufson EJ, Fahnestock M. Increased proNGF levels in subjects with mild cognitive impairment and mild Alzheimer disease. J Neuropathol Exp Neurol 2004; 63: 641-9.
184. Iulita MF, Cuello AC, Caraci F. Searching for a molecular signature of Alzheimer’s disease in Down syndrome plasma. in 12th International Conference AD/PD™. Mechanisms, Clinical Strategies, and Promising Treatments of Neurodegenerative Diseases. 2015. Nice, France: Neurodegener Dis 2015;15(suppl 1): 352-1969.