Autism as early neurodevelopmental disorder: Evidence for an sAPPamediated anabolic pathway

Frontiers in Cellular Neuroscience

Volumn , Issue MAY, 2013, Pages

  Lahiri, Debomoy K ^a,b,c   Sokol, Deborah K ^a   Erickson, Craig ^d   Ray, Balmiki ^a,c   Ho, Chang Y ^a   Maloney, Bryan ^a,c  

^a INDIANA UNIVERSITY SCHOOL OF MEDICINE   (United States)

^b Laboratory of Medical and Molecular Genetics   (United States)

^c Medical Research   (United States)

^d CINCINNATI CHILDREN'S HOSPITAL MEDICAL CENTER   (United States)

Author keywords

Alzheimer's autism continuum; Anabolic hypothesis; Cranial volume; Neurite overgrowth

Indexed keywords

ADAM PROTEIN; ADAM17 PROTEIN; AMYLOID BETA PROTEIN[1-40]; AMYLOID PRECURSOR PROTEIN; BRAIN DERIVED NEUROTROPHIC FACTOR; FRAGILE X MENTAL RETARDATION PROTEIN; MAMMALIAN TARGET OF RAPAMYCIN; METABOTROPIC RECEPTOR; MITOGEN ACTIVATED PROTEIN KINASE; PHOSPHATIDYLINOSITOL 3 KINASE; PHOSPHATIDYLINOSITOL 3,4,5 TRISPHOSPHATE 3 PHOSPHATASE; PROTEIN KINASE B; PROTEIN KINASE C; RAS PROTEIN; SECRETED AMYLOID PRECURSOR PROTEIN ALPHA; UNCLASSIFIED DRUG;

ALZHEIMER DISEASE; AUTISM; BRAIN DEVELOPMENT; BRAIN SIZE; DEVELOPMENTAL DISORDER; DNA METHYLATION; EPIGENETICS; FRAGILE X ASSOCIATED TREMOR ATAXIA SYNDROME; FRAGILE X SYNDROME; FRONTAL LOBE; GENETIC ASSOCIATION; GENETIC VARIABILITY; HUMAN; INTERNEURON; LONG TERM DEPRESSION; LONG TERM POTENTIATION; NEUROIMAGING; NEUROPATHOLOGY; NONHUMAN; NUCLEAR MAGNETIC RESONANCE IMAGING; PROTEIN PROCESSING; PROTEIN SYNTHESIS; REVIEW; TEMPORAL LOBE;

EID: 84878445323     PISSN: 16625102     EISSN: None     Source Type: Journal    
DOI: 10.3389/fncel.2013.00094     Document Type: Review

References (167)

1. (2012). Prevalence of autism spectrum disorders--Autism and Developmental Disabilities Monitoring Network, 14 sites, United States, 2008. MMWR Surveill Summ 61, 1-19.
2. Abrahams, B.S., and Geschwind, D.H. (2008). Advances in autism genetics: on the threshold of a new neurobiology. Nat Rev Genet 9, 341-355.
3. Abrahams, B.S., and Geschwind, D.H. (2010). Connecting genes to brain in the autism spectrum disorders. Arch Neurol 67, 395-399.
4. Allen-Brady, K., Miller, J., Matsunami, N., Stevens, J., Block, H., Farley, M., Krasny, L., Pingree, C., Lainhart, J., Leppert, M., Mcmahon, W.M., and Coon, H. (2009). A high- density SNP genome-wide linkage scan in a large autism extended pedigree. Mol Psychiatry 14, 590-600.
5. Allen-Brady, K., Robison, R., Cannon, D., Varvil, T., Villalobos, M., Pingree, C., Leppert, M.F., Miller, J., Mcmahon, W.M., and Coon, H. (2010). Genome-wide linkage in Utah autism pedigrees. Mol Psychiatry 15, 1006-1015.
6. Anney, R., Klei, L., Pinto, D., Regan, R., Conroy, J., Magalhaes, T.R., Correia, C., Abrahams, B.S., Sykes, N., Pagnamenta, A.T., Almeida, J., Bacchelli, E., Bailey, A.J., Baird, G., Battaglia, A., Berney, T., Bolshakova, N., Bolte, S., Bolton, P.F., Bourgeron, T., Brennan, S., Brian, J., Carson, A.R., Casallo, G., Casey, J., Chu, S.H., Cochrane, L., Corsello, C., Crawford, E.L., Crossett, A., Dawson, G., De Jonge, M., Delorme, R., Drmic, I., Duketis, E., Duque, F., Estes, A., Farrar, P., Fernandez, B.A., Folstein, S.E., Fombonne, E., Freitag, C.M., Gilbert, J., Gillberg, C., Glessner, J.T., Goldberg, J., Green, J., Guter, S.J., Hakonarson, H., Heron, E.A., Hill, M., Holt, R., Howe, J.L., Hughes, G., Hus, V., Igliozzi, R., Kim, C., Klauck, S.M., Kolevzon, A., Korvatska, O., Kustanovich, V., Lajonchere, C.M., Lamb, J.A., Laskawiec, M., Leboyer, M., Le Couteur, A., Leventhal, B.L., Lionel, A.C., Liu, X.Q., Lord, C., Lotspeich, L., Lund, S.C., Maestrini, E., Mahoney, W., Mantoulan, C., Marshall, C.R., Mcconachie, H., Mcdougle, C.J., Mcgrath, J., Mcmahon, W.M., Melhem, N.M., Merikangas, A., Migita, O., Minshew, N.J., Mirza, G.K., Munson, J., Nelson, S.F., Noakes, C., Noor, A., Nygren, G., Oliveira, G., Papanikolaou, K., Parr, J.R., Parrini, B., Paton, T., Pickles, A., Piven, J., Posey, D.J., Poustka, A., Poustka, F., et al. (2010). A genome-wide scan for common alleles affecting risk for autism. Hum Mol Genet 19, 4072-4082.
7. Arvidsson, Y., Andersson, E., Bergstrom, A., Andersson, M.K., Altiparmak, G., Illerskog, A.C., Ahlman, H., Lamazhapova, D., and Nilsson, O. (2008). Amyloid precursor-like protein 1 is differentially upregulated in neuroendocrine tumours of the gastrointestinal tract. Endocr Relat Cancer 15, 569-581.
8. Avino, T.A., and Hutsler, J.J. (2010). Abnormal cell patterning at the cortical gray-white matter boundary in autism spectrum disorders. Brain Res 1360, 138-146.
9. Aylward, E.H., Minshew, N.J., Field, K., Sparks, B.F., and Singh, N. (2002). Effects of age on brain volume and head circumference in autism. Neurology 59, 175-183.
10. Aylward, E.H., Minshew, N.J., Goldstein, G., Honeycutt, N.A., Augustine, A.M., Yates, K.O., Barta, P.E., and Pearlson, G.D. (1999). MRI volumes of amygdala and hippocampus in non-mentally retarded autistic adolescents and adults. Neurology 53, 2145-2150.
11. Bagni, C., and Greenough, W.T. (2005). From mRNP trafficking to spine dysmorphogenesis: the roots of fragile X syndrome. Nat Rev Neurosci 6, 376-387.
12. Bailey, A., Le Couteur, A., Gottesman, I., Bolton, P., Simonoff, E., Yuzda, E., and Rutter, M. (1995). Autism as a strongly genetic disorder: evidence from a British twin study. Psychol Med 25, 63-77.
13. Bailey, A., Luthert, P., Bolton, P., Le Couteur, A., Rutter, M., and Harding, B. (1993). Autism and megalencephaly. Lancet 341, 1225-1226.
14. Bailey, A.R., Giunta, B.N., Obregon, D., Nikolic, W.V., Tian, J., Sanberg, C.D., Sutton, D.T., and Tan, J. (2008). Peripheral biomarkers in Autism: secreted amyloid precursor proteinalpha as a probable key player in early diagnosis. Int J Clin Exp Med 1, 338-344.
15. Bailey, A.R., Giunta, B.N., Obregon D, Nikolic, W.V., Tian, J, Sanberg, C.D., Et Al. (2008). Peripheral biomarkers in Autism: secreted amyloid precursor protein-alpha as a probabe key player in early diagnosis. Int J Clin Exp Med. 1, 338-344.
16. Baldus, C.D., Liyanarachchi, S., Mrozek, K., Auer, H., Tanner, S.M., Guimond, M., Ruppert, A. S., Mohamed, N., Davuluri, R.V., Caligiuri, M.A., Bloomfield, C.D., and De La Chapelle, A. (2004). Acute myeloid leukemia with complex karyotypes and abnormal chromosome 21: Amplification discloses overexpression of APP, ETS2, and ERG genes. Proc Natl Acad Sci U S A 101, 3915-3920.
17. Bandyopadhyay, S., Goldstein, L.E., Lahiri, D.K., and Rogers, J.T. (2007). Role of the APP non- amyloidogenic signaling pathway and targeting alpha-secretase as an alternative drug target for treatment of Alzheimer's disease. Curr Med Chem 14, 2848-2864.
18. Barger, S.W., and Harmon, A.D. (1997). Microglial activation by Alzheimer amyloid precursor protein and modulation by apolipoprotein E. Nature 388, 878-881.
19. Bauman, M., and Kemper, T.L. (1985). Histoanatomic observations of the brain in early infantile autism. Neurology 35, 866-874.
20. Bear, M.F., Huber, K.M., and Warren, S.T. (2004). The mGluR theory of fragile X mental retardation. Trends Neurosci 27, 370-377.
21. Bell, K.F., Zheng, L., Fahrenholz, F., and Cuello, A.C. (2008). ADAM-10 over-expression increases cortical synaptogenesis. Neurobiol Aging 29, 554-565.
22. Bhaskar, K., Miller, M., Chludzinski, A., Herrup, K., Zagorski, M., and Lamb, B.T. (2009). The PI3K-Akt-mTOR pathway regulates Abeta oligomer induced neuronal cell cycle events. Mol Neurodegener 4, 14.
23. Black, R.A., Rauch, C.T., Kozlosky, C.J., Peschon, J.J., Slack, J.L., Wolfson, M.F., Castner, A.J., Stocking, K.L., Reddy, P., Srinivasan, S., Nelson, N., Boiani, N., Schooley, K.A., Gerhart, M., Davis, R., Fitzner, J.N., Johnson, R.S., Paxton, R.J., March, C.J., and Cerretti, D.P. (1997). A metalloproteinase disintegrin that releases tumour-necrosis factor-alpha from cells. Nature 385, 729-733.
24. Blumberg, S.J., Bramlett, M.D., Kogan, M.D., Schieve, L.A., and Jones, J.R. (2013). Changes in Prevalence of Parent-reported Autism Spectrum Disorder in School-aged U.S. Children: 2007 to 2011-2012, in: National Health Statistics Report. U.S. Department of Health and Human Services).
25. Buldyrev, S.V., Cruz, L., Gomez-Isla, T., Gomez-Tortosa, E., Havlin, S., Le, R., Stanley, H.E., Urbanc, B., and Hyman, B.T. (2000). Description of microcolumnar ensembles in association cortex and their disruption in Alzheimer and Lewy body dementias. Proc Natl Acad Sci U S A 97, 5039-5043.
26. Butler, M.G., Dasouki, M.J., Zhou, X.P., Talebizadeh, Z., Brown, M., Takahashi, T.N., Miles, J.H., Wang, C.H., Stratton, R., Pilarski, R., and Eng, C. (2005). Subset of individuals with autism spectrum disorders and extreme macrocephaly associated with germline PTEN tumour suppressor gene mutations. J Med Genet 42, 318-321.
27. Buxbaum, J.D., Gandy, S.E., Cicchetti, P., Ehrlich, M.E., Czernik, A.J., Fracasso, R.P., Ramabhadran, T.V., Unterbeck, A.J., and Greengard, P. (1990). Processing of Alzheimer beta/A4 amyloid precursor protein: modulation by agents that regulate protein phosphorylation. Proc Natl Acad Sci U S A 87, 6003-6006.
28. Buxhoeveden, D.P., Semendeferi, K., Buckwalter, J., Schenker, N., Switzer, R., and Courchesne, E. (2006). Reduced minicolumns in the frontal cortex of patients with autism. Neuropathol ApplNeurobiol 32, 483-491.
29. Buxhoeveden, D.P., Switala, A.E., Litaker, M., Roy, E., and Casanova, M.F. (2001). Lateralization of minicolumns in human planum temporale is absent in nonhuman primate cortex. Brain Behav Evol 57, 349-358.
30. Caporaso, G.L., Gandy, S.E., Buxbaum, J.D., Ramabhadran, T.V., and Greengard, P. (1992). Protein phosphorylation regulates secretion of Alzheimer beta/A4 amyloid precursor protein. Proc Natl Acad Sci U S A 89, 3055-3059.
31. Casanova, M.F. (2007). The neuropathology of autism. Brain Pathol 17, 422-433.
32. Casanova, M.F., Buxhoeveden, D.P., Switala, A.E., and Roy, E. (2002). Minicolumnar pathology in autism. Neurology 58, 428-432.
33. Casanova, M.F., Switala, A.E., Trippe, J., and Fitzgerald, M. (2007). Comparative minicolumnar morphometry of three distinguished scientists. Autism 11, 557-569.
34. Casanova, M.F., Van Kooten, I.A., Switala, A.E., Van Engeland, H., Heinsen, H., Steinbusch, H.W., Hof, P.R., Trippe, J., Stone, J., and Schmitz, C. (2006). Minicolumnar abnormalities in autism. Acta Neuropathol 112, 287-303.
35. Champagne, F.A., and Curley, J.P. (2009). Epigenetic mechanisms mediating the long-term effects of maternal care on development. Neurosci Biobehav Rev 33, 593-600.
36. Chan, A., and Shea, T.B. (2006). Supplementation with apple juice attenuates presenilin-1 overexpression during dietary and genetically-induced oxidative stress. J Alzheimers Dis 10, 353-358.
37. Chen, Y., and Bodles, A.M. (2007). Amyloid precursor protein modulates beta-catenin degradation. J Neuroinflammation 4, 29.
38. Cheng, G., Yu, Z., Zhou, D., and Mattson, M.P. (2002). Phosphatidylinositol-3-kinase-Akt kinase and p42/p44 mitogen-activated protein kinases mediate neurotrophic and excitoprotective actions of a secreted form of amyloid precursor protein. Exp Neurol 175, 407-414.
39. Chez, M.G., Dowling, T., Patel, P.B., Khanna, P., and Kominsky, M. (2007). Elevation of tumor necrosis factor-alpha in cerebrospinal fluid of autistic children. Pediatr Neurol 36, 361365.
40. Costa E Silva, J.A. (2008). Autism, a brain developmental disorder: some new pathopysiologic and genetics findings. Metabolism 57 Suppl 2, S40-43.
41. Courchesne, E., Carper, R., and Akshoomoff, N. (2003). Evidence of brain overgrowth in the first year of life in autism. JAMA 290, 337-344.
42. Courchesne, E., Karns, C.M., Davis, H.R., Ziccardi, R., Carper, R.A., Tigue, Z.D., Chisum, H.J., Moses, P., Pierce, K., Lord, C., Lincoln, A.J., Pizzo, S., Schreibman, L., Haas, R.H., Akshoomoff, N.A., and Courchesne, R.Y. (2001). Unusual brain growth patterns in early life in patients with autistic disorder: an MRI study. Neurology 57, 245-254.
43. Courchesne, E., and Pierce, K. (2005). Why the frontal cortex in autism might be talking only to itself: local over-connectivity but long-distance disconnection. Curr Opin Neurobiol 15, 225-230.
44. De Diego Otero, Y., Severijnen, L.A., Van Cappellen, G., Schrier, M., Oostra, B., and Willemsen, R. (2002). Transport of fragile X mental retardation protein via granules in neurites of PC12 cells. Mol Cell Biol 22, 8332-8341.
45. De Geus, E.J. (2010). From genotype to EEG endophenotype: a route for post-genomic understanding of complex psychiatric disease? Genome Med 2, 63.
46. De Rubeis, S., and Bagni, C. (2010). Fragile X mental retardation protein control of neuronal mRNA metabolism: Insights into mRNA stability. Mol Cell Neurosci 43, 43-50.
47. De Vries, B.B., Jansen, C.C., Duits, A.A., Verheij, C., Willemsen, R., Van Hemel, J.O., Van Den Ouweland, A.M., Niermeijer, M.F., Oostra, B.A., and Halley, D.J. (1996). Variable FMR1 gene methylation of large expansions leads to variable phenotype in three males from one fragile X family. J Med Genet 33, 1007-1010.
48. Demars, M.P., Bartholomew, A., Strakova, Z., and Lazarov, O. (2011).Soluble amyloid precursor protein: a novel proliferation factor of adult progenitor cells of ectodermal and mesodermal origin. Stem Cell Res Ther 2, 36.
49. Deuss, M., Reiss, K., and Hartmann, D. (2008). Part-time alpha-secretases: the functional biology of ADAM 9, 10 and 17. Curr Alzheimer Res 5, 187-201.
50. Diaz-Rodriguez, E., Montero, J.C., Esparis-Ogando, A., Yuste, L., and Pandiella, A. (2002). Extracellular signal-regulated kinase phosphorylates tumor necrosis factor alphaconverting enzyme at threonine 735: a potential role in regulated shedding. Mol Biol Cell 13, 2031-2044.
51. Dolen, G., and Bear, M.F. (2008). Role for metabotropic glutamate receptor 5 (mGluR5) in the pathogenesis of fragile X syndrome. J Physiol 586, 1503-1508.
52. Dolen, G., Osterweil, E., Rao, B.S., Smith, G.B., Auerbach, B.D., Chattarji, S., and Bear, M.F. (2007). Correction of fragile X syndrome in mice. Neuron 56, 955-962.
53. Dufault, R., Lukiw, W.J., Crider, R., Schnoll, R., Wallinga, D., and Deth, R. (2012). A macroepigenetic approach to identify factors responsible for the autism epidemic in the United States. Clinical Epigenetics 4, 6.
54. Duvall, J.A., Lu, A., Cantor, R.M., Todd, R.D., Constantino, J.N., and Geschwind, D.H. (2007). A quantitative trait locus analysis of social responsiveness in multiplex autism families. Am J Psychiatry 164, 656-662.
55. Egaas, B., Courchesne, E., and Saitoh, O. (1995). Reduced size of corpus callosum in autism. Arch Neurol 52, 794-801.
56. Erickson, C.A., Wink Lk, and Ray B.E.M., Stiegelmeyer E, Mathieu-Frasier L, Patrick V, Lahiri DK, Mcdougle CJ. (2013). Impact of acamprosate on behavior and brain-derived neurotrophic factor: an open-label study in youth with fragile X syndrome. Psychopharmacology (Berl).
57. Feng, Y., Gutekunst, C.A., Eberhart, D.E., Yi, H., Warren, S.T., and Hersch, S.M. (1997). Fragile X mental retardation protein: nucleocytoplasmic shuttling and association with somatodendritic ribosomes. J Neurosci 17, 1539-1547.
58. Flory, J.D., Bierer, L.M., and Yehuda, R. (2011).Maternal exposure to the holocaust and health complaints in offspring. Dis Markers 30, 133-139.
59. Folstein, S., and Rutter, M. (1977). Infantile autism: a genetic study of 21 twin pairs. J Child Psychol Psychiatry 18, 297-321.
60. Fuso, A., Seminara, L., Cavallaro, R.A., D'anselmi, F., and Scarpa, S. (2005). S- adenosylmethionine/homocysteine cycle alterations modify DNA methylation status with consequent deregulation of PS1 and BACE and beta-amyloid production. Mol Cell Neurosci 28, 195-204.
61. Gatz, M., Reynolds, C.A., Fratiglioni, L., Johansson, B., Mortimer, J.A., Berg, S., Fiske, A., and Pedersen, N.L. (2006). Role of genes and environments for explaining Alzheimer disease. Arch Gen Psychiatry 63, 168-174.
62. Gooz, P., Gooz, M., Baldys, A., and Hoffman, S. (2009). ADAM-17 regulates endothelial cell morphology, proliferation, and in vitro angiogenesis. Biochem Biophys Res Commun 380, 33-38.
63. Gregory, S.G., Connelly, J.J., Towers, A.J., Johnson, J., Biscocho, D., Markunas, C.A., Lintas, A., Abramson, R.K., Wright, H.H., Ellis, P., Langford, C.F., Worley, G., Delong, G.R., Murphy, S.K., Cuccaro, M.L., Persico, A., and Pericak-Vance, M.A. (2009). Genomic and epigenetic evidence for oxytocin receptor deficiency in autism. BMC Med 7, 62.
64. Grossman, A.W., Aldridge, G.M., Weiler, I.J., and Greenough, W.T. (2006). Local protein synthesis and spine morphogenesis: Fragile X syndrome and beyond. J Neurosci 26, 7151-7155.
65. Hagerman, R.J., Leehey, M., Heinrichs, W., Tassone, F., Wilson, R., Hills, J., Grigsby, J., Gage, B., and Hagerman, P.J. (2001). Intention tremor, parkinsonism, and generalized brain atrophy in male carriers of fragile X. Neurology 57, 127-130.
66. Hardy, J. (2009). The amyloid hypothesis for Alzheimer's disease: a critical reappraisal. J Neurochem 110, 1129-1134.
67. Hatton, D.D., Sideris, J., Skinner, M., Mankowski, J., Bailey, D.B., Jr., Roberts, J., and Mirrett, P. (2006). Autistic behavior in children with fragile X syndrome: prevalence, stability, and the impact of FMRP. Am J Med Genet A 140A, 1804-1813.
68. Hazlett, H.C., Poe, M.D., Gerig, G., Styner, M., Chappell, C., Smith, R.G., Vachet, C., and Piven, J. (2011). Early brain overgrowth in autism associated with an increase in cortical surface area before age 2 years. Arch Gen Psychiatry 68, 467-476.
69. Howard, T.D., Ho, S.M., Zhang, L., Chen, J., Cui, W., Slager, R., Gray, S., Hawkins, G.A., Medvedovic, M., and Wagner, J.D. (2011). Epigenetic changes with dietary soy in cynomolgus monkeys. PLoS One 6, e26791.
70. Hughes, L.A., Van Den Brandt, P.A., De Bruine, A.P., Wouters, K.A., Hulsmans, S., Spiertz, A., Goldbohm, R.A., De Goeij, A.F., Herman, J.G., Weijenberg, M.P., and Van Engeland, M. (2009). Early life exposure to famine and colorectal cancer risk: a role for epigenetic mechanisms. PLoS One 4, e7951.
71. Huttenlocher, P.R., and Hapke, R.J. (1990). A follow-up study of intractable seizures in childhood. Ann Neurol 28, 699-705.
72. Ji, L., Chauhan, A., and Chauhan, V. (2012). Reduced activity of protein kinase C in the frontal cortex of subjects with regressive autism: relationship with developmental abnormalities. Int J Biol Sci 8, 1075-1084.
73. Jiang, Y.H., Sahoo, T., Michaelis, R.C., Bercovich, D., Bressler, J., Kashork, C.D., Liu, Q., Shaffer, L.G., Schroer, R.J., Stockton, D.W., Spielman, R.S., Stevenson, R.E., and Beaudet, A.L. (2004). A mixed epigenetic/genetic model for oligogenic inheritance of autism with a limited role for UBE3A. Am J Med Genet A 131, 1-10.
74. Johnson, C.P., and Myers, S.M. (2007). Identification and evaluation of children with autism spectrum disorders. Pediatrics 120, 1183-1215.
75. Jolly-Tornetta, C., Gao, Z.Y., Lee, V.M., and Wolf, B.A. (1998). Regulation of amyloid precursor protein secretion by glutamate receptors in human Ntera 2 neurons. J Biol Chem 273, 14015-14021.
76. Jousse, C., Parry, L., Lambert-Langlais, S., Maurin, A.C., Averous, J., Bruhat, A., Carraro, V., Tost, J., Letteron, P., Chen, P., Jockers, R., Launay, J.M., Mallet, J., and Fafournoux, P. (2011). Perinatal undernutrition affects the methylation and expression of the leptin gene in adults: implication for the understanding of metabolic syndrome. FASEB J 25, 3271-3278.
77. Kaminsky, Z., Wang, S.C., and Petronis, A. (2006). Complex disease, gender and epigenetics. Ann Med 38, 530-544.
78. Kelleher, R.J., 3rd, and Bear, M.F. (2008). The autistic neuron: troubled translation? Cell 135, 401-406.
79. Kemper, T.L., and Bauman, M.L. (1993). The contribution of neuropathologic studies to the understanding of autism. Neurol Clin 11, 175-187.
80. Kennedy, D.P., Semendeferi, K., and Courchesne, E. (2007). No reduction of spindle neuron number in frontoinsular cortex in autism. Brain Cogn 64, 124-129.
81. Kerr, F., Rickle, A., Nayeem, N., Brandner, S., Cowburn, R.F., and Lovestone, S. (2006). PTEN, a negative regulator of PI3 kinase signalling, alters tau phosphorylation in cells by mechanisms independent of GSK-3. FEBSLett 580, 3121-3128.
82. Krause, K., Karger, S., Sheu, S.Y., Aigner, T., Kursawe, R., Gimm, O., Schmid, K.W., Dralle, G., and Fuhrer, D. (2008). Evidence for a role of the amyloid precursor protein in thyroid carcinogenesis. J Endocrinol 198, 291-299.
83. Lahiri, D.K., Farlow, M.R., Sambamurti, K., Greig, N.H., Giacobini, E., and Schneider, L.S. (2003). A critical analysis of new molecular targets and strategies for drug developments in Alzheimer's disease. Curr Drug Targets 4, 97-112.
84. Lahiri, D.K., Long, J.M., Ray, B. and Sokol, D.K. (2011). Biochemical Evidence for the Dysregulation of Alzheimer's Amyloid Precursor Protein (APP) Expression and Metabolism in Fragile X Syndrome (FXS) and Severe Autism, in: Society of Biological Psychiatry. (New Orleans, Louisiana).
85. Lahiri, D.K., Maloney, B., and Zawia, N.H. (2009). The LEARn model: an epigenetic explanation for idiopathic neurobiological diseases. Molecular Psychiatry 14, 992-1003.
86. Lahiri, D.K., Maloney, B., and Zawia, N.H. (2009). The LEARn model: an epigenetic explanation for idiopathic neurobiological diseases. Mol Psychiatry 14, 992-1003.
87. Lahiri, D.K., Nall, C., Chen, D., Zaphiriou, M., Morgan, C., and Nurnberger, J.I., Sr. (2002). Developmental expression of the beta-amyloid precursor protein and heat-shock protein 70 in the cerebral hemisphere region of the rat brain. Ann N Y Acad Sci 965, 324-333.
88. Landa, R. (2007). Early communication development and intervention for children with autism. Ment Retard Dev Disabil Res Rev 13, 16-25.
89. Laxova, R. (1994). Fragile X syndrome. Adv Pediatr 41, 305-342.
90. Levitt, P., and Campbell, D.B. (2009). The genetic and neurobiologic compass points toward common signaling dysfunctions in autism spectrum disorders. J Clin Invest 119, 747-754.
91. Leyssen, M., Ayaz, D., Hebert, S.S., Reeve, S., De Strooper, B., and Hassan, B.A. (2005). Amyloid precursor protein promotes post-developmental neurite arborization in the Drosophila brain. EMBO J 24, 2944-2955.
92. Li, C., Li, X., Chen, W., Yu, S., Chen, J., Wang, H., and Ruan, D. (2007). The different roles of cyclinD1-CDK4 in STP and mGluR-LTD during the postnatal development in mice hippocampus area CA1. BMC Dev Biol 7, 57.
93. Lin, P., Sun, X., Feng, T., Zou, H., Jiang, Y., Liu, Z., Zhao, D., and Yu, X. (2012). ADAM17 regulates prostate cancer cell proliferation through mediating cell cycle progression by EGFR/PI3K/AKT pathway. Mol Cell Biochem 359, 235-243.
94. Lodato, S., Rouaux, C., Quast, K.B., Jantrachotechatchawan, C., Studer, M., Hensch, T.K., and Arlotta, P. (2011). Excitatory projection neuron subtypes control the distribution of local inhibitory interneurons in the cerebral cortex. Neuron 69, 763-779.
95. Lord, C., Shulman, C., and Dilavore, P. (2004). Regression and word loss in autistic spectrum disorders. J Child Psychol Psychiatry 45, 936-955.
96. Losh, M., Sullivan, P.F., Trembath, D., and Piven, J. (2008). Current developments in the genetics of autism: from phenome to genome. JNeuropatholExp Neurol 67, 829-837.
97. Maloney, B., Sambamurti, K., Zawia, N., and Lahiri, D.K. (2012). Applying epigenetics to Alzheimer's disease via the latent early-life associated regulation (LEARn) model. Current Alzheimer Research 9, 589-599.
98. Marco, E.J., and Skuse, D.H. (2006). Autism-lessons from the X chromosome. Soc Cogn Affect Neurosci 1, 183-193.
99. Marshall, C.R., Noor, A., Vincent, J.B., Lionel, A.C., Feuk, L., Skaug, J., Shago, M., Moessner, R., Pinto, D., Ren, Y., Thiruvahindrapduram, B., Fiebig, A., Schreiber, S., Friedman, J., Ketelaars, C.E., Vos, Y.J., Ficicioglu, C., Kirkpatrick, S., Nicolson, R., Sloman, L., Summers, A., Gibbons, C.A., Teebi, A., Chitayat, D., Weksberg, R., Thompson, A., Vardy, C., Crosbie, V., Luscombe, S., Baatjes, R., Zwaigenbaum, L., Roberts, W., Fernandez, B., Szatmari, P., and Scherer, S.W. (2008). Structural variation of chromosomes in autism spectrum disorder. Am J Hum Genet 82, 477-488.
100. Martin-Gronert, M.S., and Ozanne, S.E. (2010). Mechanisms linking suboptimal early nutrition and increased risk of type 2 diabetes and obesity. J Nutr 140, 662-666.
101. Martin, G.M. (2005). Epigenetic drift in aging identical twins. Proc Natl Acad Sci U S A 102, 10413-10414.
102. Matrone, C., Di Luzio, A., Meli, G., D'aguanno, S., Severini, C., Ciotti, M.T., Cattaneo, A., and Calissano, P. (2008). Activation of the amyloidogenic route by NGF deprivation induces apoptotic death in PC12 cells. J Alzheimers Dis 13, 81-96.
103. Mattson, M.P. (1994). Secreted forms of beta-amyloid precursor protein modulate dendrite outgrowth and calcium responses to glutamate in cultured embryonic hippocampal neurons. J Neurobiol 25, 439-450.
104. Mattson, M.P. (1997). Cellular actions of beta-amyloid precursor protein and its soluble and fibrillogenic derivatives. Physiol Rev 77, 1081-1132.
105. Mattson, M.P., and Furukawa, K. (1998). Signaling events regulating the neurodevelopmental triad. Glutamate and secreted forms of beta-amyloid precursor protein as examples. Perspect Dev Neurobiol 5, 337-352.
106. Mccaffery, P., and Deutsch, C.K. (2005). Macrocephaly and the control of brain growth in autistic disorders. ProgNeurobiol 77, 38-56.
107. Mcgowan, P.O., Sasaki, A., D'alessio, A.C., Dymov, S., Labonte, B., Szyf, M., Turecki, G., and Meaney, M.J. (2009). Epigenetic regulation of the glucocorticoid receptor in human brain associates with childhood abuse. Nat Neurosci 12, 342-348.
108. Morgan, J.T., Chana, G., Pardo, C.A., Achim, C., Semendeferi, K., Buckwalter, J., Courchesne, E., and Everall, I.P. (2010). Microglial activation and increased microglial density observed in the dorsolateral prefrontal cortex in autism. Biol Psychiatry 68, 368-376.
109. Morris, L.G., Veeriah, S., and Chan, T.A. (2010). Genetic determinants at the interface of cancer and neurodegenerative disease. Oncogene 29, 3453-3464.
110. Mullan, M., and Crawford, F. (1993). Genetic and molecular advances in Alzheimer's disease. Trends Neurosci 16, 398-403.
111. Narayanan, U., Nalavadi, V., Nakamoto, M., Thomas, G., Ceman, S., Bassell, G.J., and Warren, S.T. (2008). S6K1 phosphorylates and regulates fragile X mental retardation protein (FMRP) with the neuronal protein synthesis-dependent mammalian target of rapamycin (mTOR) signaling cascade. J Biol Chem 283, 18478-18482.
112. National Fragile X Foundation (2013). Prevalence [Online]. Available: http://www.fragilex.org/fragile-x-associated-disorders/prevalence/ [Accessed February 3, 2013 2013].
113. Nelson, M.R., Wegmann, D., Ehm, M.G., Kessner, D., St Jean, P., Verzilli, C., Shen, J., Tang, Z., Bacanu, S.A., Fraser, D., Warren, L., Aponte, J., Zawistowski, M., Liu, X., Zhang, H., Zhang, Y., Li, J., Li, Y., Li, L., Woollard, P., Topp, S., Hall, M.D., Nangle, K., Wang, J., Abecasis, G., Cardon, L.R., Zollner, S., Whittaker, J.C., Chissoe, S.L., Novembre, J., and Mooser, V. (2012). An abundance of rare functional variants in 202 drug target genes sequenced in 14,002 people. Science 337, 100-104.
114. Newschaffer, C.J., Croen, L.A., Daniels, J., Giarelli, E., Grether, J.K., Levy, S.E., Mandell, D.S., Miller, L.A., Pinto-Martin, J., Reaven, J., Reynolds, A.M., Rice, C.E., Schendel, D., and Windham, G.C. (2007). The epidemiology of autism spectrum disorders. Annu Rev Public Health 28, 235-258.
115. Nickl-Jockschat, T., and Michel, T.M. (2011). The role of neurotrophic factors in autism. Mol Psychiatry 16, 478-490.
116. Nikolaev, A., Mclaughlin, T., O'leary, D.D., and Tessier-Lavigne, M. (2009). APP binds DR6 to trigger axon pruning and neuron death via distinct caspases. Nature 457, 981-989.
117. O'roak, B.J., and State, M.W. (2008). Autism genetics: strategies, challenges, and opportunities. Autism Res 1, 4-17.
118. Pennington, B.F. (2009). Diagnosing learning disorders: A neuropsychological framework. New York: Guilford Press.
119. Philippi, A., Roschmann, E., Tores, F., Lindenbaum, P., Benajou, A., Germain-Leclerc, L., Marcaillou, C., Fontaine, K., Vanpeene, M., Roy, S., Maillard, S., Decaulne, V., Saraiva, J.P., Brooks, P., Rousseau, F., and Hager, J. (2005). Haplotypes in the gene encoding protein kinase c-beta (PRKCB1) on chromosome 16 are associated with autism. Mol Psychiatry 10, 950-960.
120. Piven, J., Arndt, S., Bailey, J., and Andreasen, N. (1996). Regional brain enlargement in autism: a magnetic resonance imaging study. J Am Acad Child Adolesc Psychiatry 35, 530-536.
121. Piven, J., and Palmer, P. (1999). Psychiatric disorder and the broad autism phenotype: evidence from a family study of multiple-incidence autism families. Am J Psychiatry 156, 557-563.
122. Poot, M., Van Der Smagt, J.J., Brilstra, E.H., and Bourgeron, T. (2011). Disentangling the myriad genomics of complex disorders, specifically focusing on autism, epilepsy, and schizophrenia. Cytogenet Genome Res 135, 228-240.
123. Postina, R. (2008). A closer look at alpha-secretase. Curr Alzheimer Res 5, 179-186.
124. Poulsen, P., Esteller, M., Vaag, A., and Fraga, M.F. (2007). The epigenetic basis of twin discordance in age-related diseases. Pediatr Res 61, 38R-42R.
125. Priller, C., Bauer, T., Mitteregger, G., Krebs, B., Kretzschmar, H.A., and Herms, J. (2006). Synapse formation and function is modulated by the amyloid precursor protein. J Neurosci 26, 7212-7221.
126. Rakic, P. (1988). Defects of neuronal migration and the pathogenesis of cortical malformations. Prog Brain Res 73, 15-37.
127. Ray, B., Long, J.M., Sokol, D.K., and Lahiri, D.K. (2011). Increased secreted amyloid precursor protein-alpha (sAPPalpha) in severe autism: proposal of a specific, anabolic pathway and putative biomarker. PLoS One 6, e20405.
128. Rogers, E.J., Milhalik, S., Orthiz, D., and Shea, T.B. (2004). Apple juice prevents oxidative stress and impaired cognitive performance caused by genetic and dietary deficiencies in mice. JNutr Health Aging 8, 92-97.
129. Rohe, M., Carlo, A.S., Breyhan, H., Sporbert, A., Militz, D., Schmidt, V., Wozny, C., Harmeier, A., Erdmann, B., Bales, K.R., Wolf, S., Kempermann, G., Paul, S.M., Schmitz, D., Bayer, T.A., Willnow, T.E., and Andersen, O.M. (2008). Sortilin-related receptor with A- type repeats (SORLA) affects the amyloid precursor protein-dependent stimulation of ERK signaling and adult neurogenesis. J Biol Chem 283, 14826-14834.
130. Rutter, M. (2000). Genetic studies of autism: from the 1970s into the millennium. J Abnorm Child Psychol 28, 3-14.
131. Ruzzo, E.K., Pappas, A.L., and Goldstein, D.B. (2012). Modifier genetics in neuropsychiatric disease: challenges and opportunities. Genome Biol 13, 150.
132. Santos, M., Uppal, N., Butti, C., Wicinski, B., Schmeidler, J., Giannakopoulos, P., Heinsen, H., Schmitz, C., and Hof, P.R. (2011). Von Economo neurons in autism: a stereologic study of the frontoinsular cortex in children. Brain Res 1380, 206-217.
133. Schubert, D., Jin, L.W., Saitoh, T., and Cole, G. (1989). The regulation of amyloid beta protein precursor secretion and its modulatory role in cell adhesion. Neuron 3, 689-694.
134. Schumann, C.M., and Amaral, D.G. (2006). Stereological analysis of amygdala neuron number in autism. J Neurosci 26, 7674-7679.
135. Schumann, C.M., Bloss, C.S., Barnes, C.C., Wideman, G.M., Carper, R.A., Akshoomoff, N., Pierce, K., Hagler, D., Schork, N., Lord, C., and Courchesne, E. (2010). Longitudinal Magnetic Resonance Imaging Study of Cortical Development through Early Childhood in Autism. J. Neurosci. 30, 4419-4427.
136. Schumann, C.M., Hamstra, J., Goodlin-Jones, B.L., Lotspeich, L.J., Kwon, H., Buonocore, M.H., Lammers, C.R., Reiss, A.L., and Amaral, D.G. (2004). The amygdala is enlarged in children but not adolescents with autism; the hippocampus is enlarged at all ages. J Neurosci 24, 6392-6401.
137. Schumann, C.M., and Nordahl, C.W. (2011). Bridging the gap between MRI and postmortem research in autism. Brain Res 1380, 175-186.
138. Shulha, H.P., Cheung, I., Whittle, C., Wang, J., Virgil, D., Lin, C.L., Guo, Y., Lessard, A., Akbarian, S., and Weng, Z. (2012). Epigenetic Signatures of Autism: Trimethylated H3K4 Landscapes in Prefrontal Neurons. Arch Gen Psychiatry 69, 314-324.
139. Siemes, C., Quast, T., Klein, E., Bieber, T., Hooper, N.M., and Herzog, V. (2004). Normalized proliferation of normal and psoriatic keratinocytes by suppression of sAPPalpha-release. J Invest Dermatol 123, 556-563.
140. Sokol, D.K., Chen, D., Farlow, M.R., Dunn, D.W., Maloney, B., Zimmer, J.A., and Lahiri, D.K. (2006). High levels of Alzheimer beta-amyloid precursor protein (APP) in children with severely autistic behavior and aggression. J Child Neurol 21, 444-449.
141. Sokol, D.K., and Edwards-Brown, M. (2004). Neuroimaging in autistic spectrum disorder (ASD). J Neuroimaging 14, 8-15.
142. Sokol, D.K., and Lahiri, D.K. (2011). The Genetics of Autism, in International Handbook of Autism and Pervasive Developmental Disorders, eds. J.L. Matson & P. Sturmey. (New York: Springer), 77-127.
143. Sokol, D.K., Maloney, B., Long, J.M., Ray, B., and Lahiri, D.K. (2011). Autism, Alzheimer disease, and fragile X: APP, FMRP, and mGluR5 are molecular links. Neurology 76, 1344-1352.
144. Sparks, B.F., Friedman, S.D., Shaw, D.W., Aylward, E.H., Echelard, D., Artru, A.A., Maravilla, K.R., Giedd, J.N., Munson, J., Dawson, G., and Dager, S.R. (2002). Brain structural abnormalities in young children with autism spectrum disorder. Neurology 59, 184-192.
145. Stanfield, A.C., Mcintosh, A.M., Spencer, M.D., Philip, R., Gaur, S., and Lawrie, S.M. (2008). Towards a neuroanatomy of autism: a systematic review and meta-analysis of structural magnetic resonance imaging studies. Eur Psychiatry 23, 289-299.
146. Steffenburg, S., Gillberg, C., Hellgren, L., Andersson, L., Gillberg, I.C., Jakobsson, G., and Bohman, M. (1989). A twin study of autism in Denmark, Finland, Iceland, Norway and Sweden. J Child Psychol Psychiatry 30, 405-416.
147. Stein, T.D., and Johnson, J.A. (2003). Genetic programming by the proteolytic fragments of the amyloid precursor protein: somewhere between confusion and clarity. Rev Neurosci 14, 317-341.
148. Sucksmith, E., Roth, I., and Hoekstra, R.A. (2011). Autistic traits below the clinical threshold: re-examining the broader autism phenotype in the 21st century. Neuropsychol Rev 21, 360-389.
149. Szyf, M. (2007). The dynamic epigenome and its implications in toxicology. Toxicol Sci 100, 723.
150. Thinakaran, G., and Koo, E.H. (2008). Amyloid precursor protein trafficking, processing, and function. J Biol Chem 283, 29615-29619.
151. Trollope, A.F., Gutierrez-Mecinas, M., Mifsud, K.R., Collins, A., Saunderson, E.A., and Reul, J.M. (2012). Stress, epigenetic control of gene expression and memory formation. Exp Neurol 233, 3-11.
152. Turner, P.R., O'connor, K., Tate, W.P., and Abraham, W.C. (2003). Roles of amyloid precursor protein and its fragments in regulating neural activity, plasticity and memory. Prog Neurobiol 70, 1-32.
153. Van Kooten, I.A., Palmen, S.J., Von Cappeln, P., Steinbusch, H.W., Korr, H., Heinsen, H., Hof, P.R., Van Engeland, H., and Schmitz, C. (2008). Neurons in the fusiform gyrus are fewer and smaller in autism. Brain 131, 987-999.
154. Vanderklish, P.W., and Edelman, G.M. (2002). Dendritic spines elongate after stimulation of group 1 metabotropic glutamate receptors in cultured hippocampal neurons. Proc Natl Acad Sci US A 99, 1639-1644.
155. Vargas, D.L., Nascimbene, C., Krishnan, C., Zimmerman, A.W., and Pardo, C.A. (2005). Neuroglial activation and neuroinflammation in the brain of patients with autism. Ann Neurol 57, 67-81.
156. Venezia, V., Nizzari, M., Repetto, E., Violani, E., Corsaro, A., Thellung, S., Villa, V., Carlo, P., Schettini, G., Florio, T., and Russo, C. (2006). Amyloid precursor protein modulates ERK-1 and -2 signaling. Ann N Y Acad Sci 1090, 455-465.
157. Vingtdeux, V., and Marambaud, P. (2012). Identification and biology of alpha-secretase. J Neurochem 120 Suppl 1, 34-45.
158. Vorstman, J.A., Staal, W.G., Van Daalen, E., Van Engeland, H., Hochstenbach, P.F., and Franke, L. (2006). Identification of novel autism candidate regions through analysis of reported cytogenetic abnormalities associated with autism. Mol Psychiatry 11, 1, 18-28.
159. Vrotsos, E.G., and Sugaya, K. (2009). MCP-1-induced migration of NT2 neuroprogenitor cells involving APP signaling. Cell Mol Neurobiol 29, 373-381.
160. Wang, S.C., Oelze, B., and Schumacher, A. (2008). Age-specific epigenetic drift in late-onset Alzheimer's disease. PLoS One 3, e2698.
161. Wegiel, J., Kuchna, I., Nowicki, K., Imaki, H., Marchi, E., Ma, S.Y., Chauhan, A., Chauhan, V., Bobrowicz, T.W., De Leon, M., Louis, L.A., Cohen, I.L., London, E., Brown, W.T., and Wisniewski, T. (2010). The neuropathology of autism: defects of neurogenesis and neuronal migration, and dysplastic changes. Acta Neuropathol 119, 755-770.
162. Wehner, S., Siemes, C., Kirfel, G., and Herzog, V. (2004). Cytoprotective function of sAppalpha in human keratinocytes. Eur J Cell Biol 83, 701-708.
163. Westmark, C.J., and Malter, J.S. (2007). FMRP mediates mGluR5-dependent translation of amyloid precursor protein. PLoS Biol 5, e52.
164. Wu, J., Basha, M.R., and Zawia, N.H. (2008). The environment, epigenetics and amyloidogenesis. J Mol Neurosci 34, 1-7.
165. Xiao, L.J., Lin, P., Lin, F., Liu, X., Qin, W., Zou, H.F., Guo, L., Liu, W., Wang, S.J., and Yu, X.G. (2012). ADAM17 targets MMP-2 and MMP-9 via EGFR-MEK-ERK pathway activation to promote prostate cancer cell invasion. Int J Oncol 40, 1714-1724.
166. Young-Pearse, T.L., Bai, J., Chang, R., Zheng, J.B., Loturco, J.J., and Selkoe, D.J. (2007). A critical function for beta-amyloid precursor protein in neuronal migration revealed by in utero RNA interference. J Neurosci 27, 14459-14469.
167. Zheng, X., Jiang, F., Katakowski, M., Lu, Y., and Chopp, M. (2012). ADAM17 promotes glioma cell malignant phenotype. Mol Carcinog 51, 150-164.