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Handbook of Neurochemistry and Molecular Neurobiology pp 147–155Cite as

Parallels Between Neurodevelopment and Neurodegeneration: A Case Study of Alzheimer's Disease

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Abstract:

An accumulating body of evidence shows significant similarities between cellular processes involved in neurodegeneration and those involved in neurodevelopment. Most striking, in Alzheimer's disease, cell cycle re‐entry appears to be a pathological signature of the disease that also occur in brain development. Such inappropriate reactivation of a fetal program is likely to play a key role in both the etiology and pathogenesis of disease.

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Abbreviations

AD:

Alzheimer's disease

ApoE:

apolipoprotein E

AβPP:

amyloid‐β protein precursor

Aβ:

amyloid‐β

Cdk:

cyclin‐dependent kinase

HPG axis:

hypothalamic‐pituitary‐gonadal axis

HRT:

hormone replacement therapy

LH:

luteinizing hormone

PS:

presenilin

ROS:

reactive oxygen species

References

  • Al-Hader AA, Lei ZM, Rao CV. 1997a. Novel expression of functional luteinizing hormone/chorionic gonadotropin receptors in cultured glial cells from neonatal rat brains. Biol Reprod 56: 501–507.

    Article  CAS  Google Scholar 

  • Al-Hader AA, Lei ZM, Rao CV. 1997b. Neurons from fetal rat brains contain functional luteinizing hormone/chorionic gonadotropin receptors. Biol Reprod 56: 1071–1076.

    Article  CAS  Google Scholar 

  • Allen SJ, MacGowan SH, Treanor JJ, Feeney R, Wilcock GK, et al. 1991. Normal beta-NGF content in Alzheimer's disease cerebral cortex and hippocampus. Neurosci Lett 131: 135–139.

    Article  CAS  PubMed  Google Scholar 

  • Birecree E, Whetsell WO Jr, Stoscheck C, King LE Jr, Nanney LB. 1988. Immunoreactive epidermal growth factor receptors in neuritic plaques from patients with Alzheimer's disease. J Neuropathol Exp Neurol 47: 549–560.

    Article  CAS  PubMed  Google Scholar 

  • Bothwell M, Giniger E. 2000. Alzheimer's disease: Neurodevelopment converges with neurodegeneration. Cell 102: 271–273.

    Article  CAS  PubMed  Google Scholar 

  • Bowen RL. 2001. Sex hormones, amyloid protein, and Alzheimer disease. JAMA 286: 790–791.

    Article  CAS  PubMed  Google Scholar 

  • Bowen RL, Isley JP, Atkinson RL. 2000. An association of elevated serum gonadotropin concentrations and Alzheimer disease? J Neuroendocrinol 12: 351–354.

    Article  CAS  PubMed  Google Scholar 

  • Bowen RL, Smith MA, Harris PL, Kubat Z, Martins RN, et al. 2002. Elevated luteinizing hormone expression colocalizes with neurons vulnerable to Alzheimer's disease pathology. J Neurosci Res 70: 514–518.

    Article  CAS  PubMed  Google Scholar 

  • Breitner JC, Silverman JM, Mohs RC, Davis KL. 1988. Familial aggregation in Alzheimer's disease: Comparison of risk among relatives of early-and late-onset cases, and among male and female relatives in successive generations. Neurology 38: 207–212.

    CAS  PubMed  Google Scholar 

  • Bruni P, Minopoli G, Brancaccio T, Napolitano M, Faraonio R, et al. 2002. Fe65, a ligand of the Alzheimer's beta-amyloid precursor protein, blocks cell cycle progression by down-regulating thymidylate synthase expression. J Biol Chem 277: 35481–35488.

    Article  CAS  PubMed  Google Scholar 

  • Busser J, Geldmacher DS, Herrup K. 1998. Ectopic cell cycle proteins predict the sites of neuronal cell death in Alzheimer's disease brain. J Neurosci 18: 2801–2807.

    CAS  PubMed  Google Scholar 

  • Chen Y, McPhie DL, Hirschberg J, Neve RL. 2000. The amyloid precursor protein-binding protein APP-BP1 drives the cell cycle through the S-M checkpoint and causes apoptosis in neurons. J Biol Chem 275: 8929–8935.

    Article  CAS  PubMed  Google Scholar 

  • Chenn A, Walsh CA. 2002. Regulation of cerebral cortical size by control of cell cycle exit in neural precursors. Science 297: 365–369.

    Article  CAS  PubMed  Google Scholar 

  • Connor B, Young D, Lawlor P, Gai W, Waldvogel H, et al. 1996. Trk receptor alterations in Alzheimer's disease. Mol Brain Res 42: 1–17.

    Article  CAS  PubMed  Google Scholar 

  • Connor B, Beilharz EJ, Williams C, Synek B, Gluckman PD, et al. 1997. Insulin-like growth factor-I (IGF-I) immunoreactivity in the Alzheimer's disease temporal cortex and hippocampus. Mol Brain Res 49: 283–290.

    Article  CAS  PubMed  Google Scholar 

  • Copani A, Condorelli F, Caruso A, Vancheri C, Sala A, et al. 1999. Mitotic signaling by beta-amyloid causes neuronal death. FASEB J 13: 2225–2234.

    CAS  PubMed  Google Scholar 

  • Coulson EJ, Paliga K, Beyreuther K, Masters CL. 2000. What the evolution of the amyloid protein precursor supergene family tells us about its function. Neurochem Int 36: 175–184.

    Article  CAS  PubMed  Google Scholar 

  • Cross CE, Halliwell B, Borish ET, Pryor WA, Ames BN, et al. 1987. Oxygen radicals and human disease. Ann Intern Med 107: 526–545.

    CAS  PubMed  Google Scholar 

  • Crutcher KA, Scott SA, Liang S, Everson WV, Weingartner J. 1993. Detection of NGF-like activity in human brain tissue: Increased levels in Alzheimer's disease. J Neurosci 13: 2540–2550.

    CAS  PubMed  Google Scholar 

  • Fenton H, Finch PW, Rubin JS, Rosenberg JM, Taylor WG, et al. 1998. Hepatocyte growth factor (HGF/SF) in Alzheimer's disease. Brain Res 779: 262–270.

    Article  CAS  PubMed  Google Scholar 

  • Ferguson KL, Callaghan SM, O'Hare MJ, Park DS, Slack RS. 2000. The Rb-CDK4/6 signaling pathway is critical in neural precursor cell cycle regulation. J Biol Chem 275: 33593–33600.

    Article  CAS  PubMed  Google Scholar 

  • Fossgreen A, Bruckner B, Czech C, Masters CL, Beyreuther K, et al. 1998. Transgenic Drosophila expressing human amyloid precursor protein show gamma-secretase activity and a blistered-wing phenotype. Proc Natl Acad Sci USA 95: 13703–13708.

    Article  CAS  PubMed  Google Scholar 

  • Gomez-Pinilla F, Cummings BJ, Cotman CW. 1990. Induction of basic fibroblast growth factor in Alzheimer's disease pathology. Neuroreport 1: 211–214.

    Article  CAS  PubMed  Google Scholar 

  • Hardy J. 1997. Amyloid, the presenilins and Alzheimer's disease. Trends Neurosci 20: 154–159.

    Article  CAS  PubMed  Google Scholar 

  • Harris D, Bonfil D, Chuderland D, Kraus S, Seger R, et al. 2002. Activation of MAPK cascades by GnRH: ERK and Jun N-terminal kinase are involved in basal and GnRH-stimulated activity of the glycoprotein hormone LHbeta-subunit promoter. Endocrinology 143: 1018–1025.

    Article  CAS  PubMed  Google Scholar 

  • Heber S, Herms J, Gajic V, Hainfellner J, Aguzzi A, et al. 2000. Mice with combined gene knock-outs reveal essential and partially redundant functions of amyloid precursor protein family members. J Neurosci 20: 7951–7963.

    CAS  PubMed  Google Scholar 

  • Henderson VW, Paganini-Hill A, Emanuel CK, Dunn ME, Buckwalter JG. 1994. Estrogen replacement therapy in older women. Comparisons between Alzheimer's disease cases and nondemented control subjects. Arch Neurol 51: 896–900.

    CAS  PubMed  Google Scholar 

  • Hirai K, Aliev G, Nunomura A, Fujioka H, Russell RL, et al. 2001. Mitochondrial abnormalities in Alzheimer's disease. J Neurosci 21: 3017–3023.

    CAS  PubMed  Google Scholar 

  • Hoffmann J, Twiesselmann C, Kummer MP, Romagnoli P, Herzog V. 2000. A possible role for the Alzheimer amyloid precursor protein in the regulation of epidermal basal cell proliferation. Eur J Cell Biol 79: 905–914.

    Article  CAS  PubMed  Google Scholar 

  • Janicki SM, Monteiro MJ. 1999. Presenilin overexpression arrests cells in the G1 phase of the cell cycle. Arrest potentiated by the Alzheimer's disease PS2(N141I)mutant. Am J Pathol 155: 135–144.

    CAS  PubMed  Google Scholar 

  • Janicki SM, Stabler SM, Monteiro MJ. 2000. Familial Alzheimer's disease presenilin-1 mutants potentiate cell cycle arrest. Neurobiol Aging 21: 829–836.

    Article  CAS  PubMed  Google Scholar 

  • Jorm AF, Jolley D. 1998. The incidence of dementia: A meta-analysis. Neurology 51: 728–733.

    CAS  PubMed  Google Scholar 

  • Jorm AF, Korten AE, Henderson AS. 1987. The prevalence of dementia: A quantitative integration of the literature. Acta Psychiatr Scand 76: 465–479.

    Article  CAS  PubMed  Google Scholar 

  • Kang DE, Soriano S, Xia X, Eberhart CG, De Strooper B, et al. 2002. Presenilin couples the paired phosphorylation of beta-catenin independent of axin: Implications for beta-catenin activation in tumorigenesis. Cell 110: 751–762.

    Article  CAS  PubMed  Google Scholar 

  • Kawas C, Resnick S, Morrison A, Brookmeyer R, Corrada M, et al. 1997. A prospective study of estrogen replacement therapy and the risk of developing Alzheimer's disease: The Baltimore longitudinal study of aging. Neurology 48: 1517–1521.

    CAS  PubMed  Google Scholar 

  • Koo EH. 2002. The beta-amyloid precursor protein (APP) and Alzheimer's disease: Does the tail wag the dog? Traffic 3: 763–770.

    Article  CAS  PubMed  Google Scholar 

  • Lei ZM, Rao CV, Kornyei JL, Licht P, Hiatt ES. 1993. Novel expression of human chorionic gonadotropin/luteinizing hormone receptor gene in brain. Endocrinology 132: 2262–2270.

    Article  CAS  PubMed  Google Scholar 

  • Li J, Xu M, Zhou H, Ma J, Potter H. 1997. Alzheimer presenilins in the nuclear membrane, interphase kinetochores, and centrosomes suggest a role in chromosome segregation. Cell 90: 917–927.

    Article  CAS  PubMed  Google Scholar 

  • Lukacs H, Hiatt ES, Lei ZM, Rao CV. 1995. Peripheral and intracerebroventricular administration of human chorionic gonadotropin alters several hippocampus-associated behaviors in cycling female rats. Horm Behav 29: 42–58.

    Article  CAS  PubMed  Google Scholar 

  • Manly JJ, Merchant CA, Jacobs DM, Small SA, Bell K, et al. 2000. Endogenous estrogen levels and Alzheimer's disease among postmenopausal women. Neurology 54: 833–837.

    CAS  PubMed  Google Scholar 

  • Masliah E, Mallory M, Alford M, Deteresa R, Saitoh T. 1995. PDGF is associated with neuronal and glial alterations of Alzheimer's disease. Neurobiol Aging 16: 549–556.

    Article  CAS  PubMed  Google Scholar 

  • McGonigal G, Thomas B, McQuade C, Starr JM, MacLennan WJ, et al. 1993. Epidemiology of Alzheimer's presenile dementia in Scotland, 1974–88. BMJ 306: 680–683.

    Article  CAS  PubMed  Google Scholar 

  • McShea A, Harris PL, Webster KR, Wahl AF, Smith MA. 1997. Abnormal expression of the cell cycle regulators P16 and CDK4 in Alzheimer's disease. Am J Pathol 150: 1933–1939.

    CAS  PubMed  Google Scholar 

  • Milward EA, Papadopoulos R, Fuller SJ, Moir RD, Small D, et al. 1992. The amyloid protein precursor of Alzheimer's disease is a mediator of the effects of nerve growth factor on neurite outgrowth. Neuron 9: 129–137.

    Article  CAS  PubMed  Google Scholar 

  • Mulnard RA. 2000. Estrogen as a treatment for Alzheimer disease. JAMA 284: 307–308.

    Article  PubMed  Google Scholar 

  • Mulnard RA, Cotman CW, Kawas C, van Dyck CH, Sano M, et al. 2000. Estrogen replacement therapy for treatment of mild to moderate Alzheimer disease: A randomized controlled trial. Alzheimer's disease cooperative study. JAMA 283: 1007–1015.

    Article  CAS  PubMed  Google Scholar 

  • Nagy Z, Esiri MM, Smith AD. 1997a. Expression of cell division markers in the hippocampus in Alzheimer's disease and other neurodegenerative conditions. Acta Neuropathol (Berl) 93: 294–300.

    Article  CAS  Google Scholar 

  • Nagy Z, Esiri MM, Cato AM, Smith AD. 1997b. Cell cycle markers in the hippocampus in Alzheimer's disease. Acta Neuropathol (Berl) 94: 6–15.

    Article  CAS  Google Scholar 

  • Nunomura A, Perry G, Aliev G, Hirai K, Takeda A, et al. 2001. Oxidative damage is the earliest event in Alzheimer disease. J Neuropathol Exp Neurol 60: 759–767.

    CAS  PubMed  Google Scholar 

  • Ogawa O, Lee HG, Zhu X, Raina A, Harris PL, et al. 2003. Increased p27, an essential component of cell cycle control, in Alzheimer's disease. Aging Cell 2: 105–110.

    Article  CAS  PubMed  Google Scholar 

  • Perry G, Castellani RJ, Hirai K, Smith MA. 1998. Reactive oxygen species mediate cellular damage in Alzheimer disease. J Alzheimers Dis 1: 45-55.

    CAS  PubMed  Google Scholar 

  • Raina AK, Zhu X, Rottkamp CA, Monteiro M, Takeda A, et al. 2000. Cyclin' toward dementia: Cell cycle abnormalities and abortive oncogenesis in Alzheimer disease. J Neurosci Res 61: 128–133.

    Article  CAS  PubMed  Google Scholar 

  • Rapp SR, Espeland MA, Shumaker SA, Henderson VW, Brunner RL, et al. 2003. Effect of estrogen plus progestin on global cognitive function in postmenopausal women: The Women's Health Initiative memory study: A randomized controlled trial. JAMA 289: 2663–2672.

    Article  CAS  PubMed  Google Scholar 

  • Resnick SM, Henderson VW. 2002. Hormone therapy and risk of Alzheimer disease: A critical time. JAMA 288: 2170–2172.

    Article  PubMed  Google Scholar 

  • Rocca WA, Hofman A, Brayne C, Breteler MM, Clarke M, et al. 1991. Frequency and distribution of Alzheimer's disease in Europe: A collaborative study of 1980–1990 prevalence findings. The EURODEM-Prevalence Research Group. Ann Neurol 30: 381–390.

    Article  CAS  PubMed  Google Scholar 

  • Schmitz A, Tikkanen R, Kirfel G, Herzog V. 2002. The biological role of the Alzheimer amyloid precursor protein in epithelial cells. Histochem Cell Biol 117: 171–180.

    Article  CAS  PubMed  Google Scholar 

  • Schubert D, Cole G, Saitoh T, Oltersdorf T. 1989. Amyloid beta protein precursor is a mitogen. Biochem Biophys Res Commun 162: 83–88.

    Article  CAS  PubMed  Google Scholar 

  • Schupf N, Kapell D, Nightingale B, Rodriguez A, Tycko B, et al. 1998. Earlier onset of Alzheimer's disease in men with Down syndrome. Neurology 50: 991–995.

    CAS  PubMed  Google Scholar 

  • Selkoe D, Kopan R. 2003. Notch and Presenilin: Regulated intramembrane proteolysis links development and degeneration. Annu Rev Neurosci 26: 565–597.

    Article  CAS  PubMed  Google Scholar 

  • Shen J, Bronson RT, Chen DF, Xia W, Selkoe DJ, et al. 1997. Skeletal and CNS defects in Presenilin-1-deficient mice. Cell 89: 629–639.

    Article  CAS  PubMed  Google Scholar 

  • Short RA, Bowen RL, O'Brien PC, Graff-Radford NR. 2001. Elevated gonadotropin levels in patients with Alzheimer disease. Mayo Clin Proc 76: 906–909.

    Article  CAS  PubMed  Google Scholar 

  • Smith TW, Lippa CF. 1995. Ki-67 immunoreactivity in Alzheimer's disease and other neurodegenerative disorders. J Neuropathol Exp Neurol 54: 297–303.

    Article  CAS  PubMed  Google Scholar 

  • Smith MA, Perry G, Atwood CS, Bowen RL. 2003. Estrogen replacement and risk of Alzheimer disease. JAMA 289: 1100.

    Article  PubMed  Google Scholar 

  • Soriano S, Kang DE, Fu M, Pestell R, Chevallier N, et al. 2001. Presenilin 1 negatively regulates beta-catenin/T cell factor/lymphoid enhancer factor-1 signaling independently of beta-amyloid precursor protein and notch processing. J Cell Biol 152: 785–794.

    Article  CAS  PubMed  Google Scholar 

  • Stopa EG, Gonzalez AM, Chorsky R, Corona RJ, Alvarez J, et al. 1990. Basic fibroblast growth factor in Alzheimer's disease. Biochem Biophys Res Commun 171: 690–696.

    Article  CAS  PubMed  Google Scholar 

  • Styren SD, Mufson EJ, Styren GC, Civin WH, Rogers J. 1990. Epidermal growth factor receptor expression in demented and aged human brain. Brain Res 512: 347–352.

    Article  CAS  PubMed  Google Scholar 

  • Tang MX, Jacobs D, Stern Y, Marder K, Schofield P, et al. 1996. Effect of oestrogen during menopause on risk and age at onset of Alzheimer's disease. Lancet 348: 429–432.

    Article  CAS  PubMed  Google Scholar 

  • Tham A, Nordberg A, Grissom FE, Carlsson-Skwirut C, Viitanen M, et al. 1993. Insulin-like growth factors and insulin-like growth factor binding proteins in cerebrospinal fluid and serum of patients with dementia of the Alzheimer type. J Neural Transm Park Dis Dement Sect 5: 165–176.

    Article  CAS  PubMed  Google Scholar 

  • Vincent I, Jicha G, Rosado M, Dickson DW. 1997. Aberrant expression of mitotic cdc2/cyclin B1 kinase in degenerating neurons of Alzheimer's disease brain. J Neurosci 17: 3588–3598.

    CAS  PubMed  Google Scholar 

  • Vincent I, Zheng JH, Dickson DW, Kress Y, Davies P. 1998. Mitotic phosphoepitopes precede paired helical filaments in Alzheimer's disease. Neurobiol Aging 19: 287–296.

    Article  CAS  PubMed  Google Scholar 

  • Willert K, Nusse R. 1998. Beta-catenin: A key mediator of Wnt signaling. Curr Opin Genet Dev 8: 95–102.

    Article  CAS  PubMed  Google Scholar 

  • Wong PC, Zheng H, Chen H, Becher MW, Sirinathsinghji DJ, et al. 1997. Presenilin 1 is required for Notch1 and DII1 expression in the paraxial mesoderm. Nature 387: 288–292.

    Article  CAS  PubMed  Google Scholar 

  • Yang Y, Geldmacher DS, Herrup K. 2001. DNA replication precedes neuronal cell death in Alzheimer's disease. J Neurosci 21: 2661–2668.

    CAS  PubMed  Google Scholar 

  • Yang Y, Mufson EJ, Herrup K. 2003. Neuronal cell death is preceded by cell cycle events at all stages of Alzheimer's disease. J Neurosci 23: 2557–2563.

    CAS  PubMed  Google Scholar 

  • Yuasa S, Nakajima M, Aizawa H, Sahara N, Koizumi K, et al. 2002. Impaired cell cycle control of neuronal precursor cells in the neocortical primordium of presenilin-1-deficient mice. J Neurosci Res 70: 501–513.

    Article  CAS  PubMed  Google Scholar 

  • Zhu X, Rottkamp CA, Raina AK, Brewer GJ, Ghanbari HA, et al. 2000. Neuronal CDK7 in hippocampus is related to aging and Alzheimer disease. Neurobiol Aging 21: 807–813.

    Article  CAS  PubMed  Google Scholar 

  • Zhu X, Raina AK, Perry G, Smith MA. 2004a. Alzheimer's disease: The two-hit hypothesis. Lancet Neurol 3: 219–226.

    Article  CAS  Google Scholar 

  • Zhu X, McShea A, Harris PLR, Raina AK, Castellani RJ, et al. 2004b. Elevated expression of a regulator of the G2/M phase of the cell cycle, neuronal CIP-1 associated regulator of cyclin B, in Alzheimer's disease. J Neurosci Res 75: 698–703.

    Article  CAS  Google Scholar 

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Acknowledgements

Work in the authors' laboratories is supported by the National Institutes of Health and the Alzheimer's Association. CSA, GP, and MAS are consultants for and own equity in Voyager Pharmaceutical Corporation.

Authors
  1. X. Zhu
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  2. G. Casadesus
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  3. K. M. Webber
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  4. C. S. Atwood
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  5. R. L. Bowen
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  6. G. Perry
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  7. M. A. Smith
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Editor information

Editors and Affiliations

  1. Center for Neurochemistry, Nathan S. Kline Institute for Psychiatric Research, 10962, 140 Old Orangeburg Road, Orangeburg, New York, USA

    Abel Lajtha (Director) (Director)

  2. Department of Biochemistry & Molecular Biology, University of Texas Medical Branch, 301 University Blvd., TX, 77555, Galveston, USA

    J. Regino Perez-Polo (I. H. Kempner Professor and Chair Dept. Biochemistry & Molecular Biology Senior Scientist Sealy Center for Molecular Medicine Staff Scientist Shriner's Hospital for Children) (I. H. Kempner Professor and Chair Dept. Biochemistry & Molecular Biology Senior Scientist Sealy Center for Molecular Medicine Staff Scientist Shriner's Hospital for Children)

  3. Universität Leipzig Medizinische Fakultät, Paul-Flechsig-Institut für Hirnforschung, Jahnallee 59, 04109, Leipzig, Germany

    Steffen Rossner

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Zhu, X. et al. (2008). Parallels Between Neurodevelopment and Neurodegeneration: A Case Study of Alzheimer's Disease. In: Lajtha, A., Perez-Polo, J.R., Rossner, S. (eds) Handbook of Neurochemistry and Molecular Neurobiology. Springer, Boston, MA. https://doi.org/10.1007/978-0-387-32671-9_7

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