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Dementias pp 19-50 | Cite as

The Biological Basis of Dementias

  • M. Racchi
  • S. Govoni

Abstract

In this chapter we review briefly the state of the art of research on the molecular mechanisms that underlie neurodegenerative dementing illnesses. There is still no cure for any of the dementing neurodegenerative diseases that lead to some form of dementia. Most of the treatments proposed for Alzheimer’s disease (AD) and other dementias are, by design, effective only in ameliorating symptoms of the disease and, at best, slowing the pace of progression. The time of intervention, due to the complexity of early diagnosis, is often late with respect to the biological onset of the disease and therefore limits the final efficacy of the treatment. In neurodegenerative diseases where the progression of degeneration can be slowed, possibly stopped but theoretically not reversed, the time of intervention is an extremely important issue. Searching for the molecular and biological basis of dementing disorders provides an opportunity to identify targets of pharmacological intervention. Early biochemical markers of the onset of the disease could allow treatment at early stages; identification of genetic risk factors can direct new efforts at studying molecular targets for prevention. Clinical variability among populations of affected patients is certainly due to differences in genetic and biochemical backgrounds, and these can also account for the differences in effectiveness of therapeutic intervention. Only molecular dissection of the pathogenetic processes can provide the information needed to increase the likelihood that a specific treatment will be effective.

Keywords

Lewy Body Prion Protein Prion Disease PRNP Gene Fatal Familial Insomnia 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.

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References

  1. 1.
    Terry RD, Peck A, De Teresa R, et al (1981) Some morphometric aspects of the brain in senile dementia of the Alzheimer type. Ann Neurol 10: 184–192PubMedCrossRefGoogle Scholar
  2. 2.
    Vereecken TH, Vogels OJ, Nieuwenhuys R (1994) Neuron loss and shrinkage in the amygdala in Alzheimer’s disease. Neurobiol Aging 15: 45–54PubMedCrossRefGoogle Scholar
  3. 3.
    Leuba G, Kraftisik R (1994) Visual cortex in Alzheimer’s disease: occurrence of neuronal death and glial proliferation, and correlation with pathological hallmarks. Neurobiol Aging 15: 29–43PubMedCrossRefGoogle Scholar
  4. 4.
    Vogels OJM, Broere CAJ, ter Laak HJ, et al (1990) Cell loss and shrinkage in the nucleus basalis Meynert complex in Alzheimer’s disease. Neurobiol Aging 11: 3–13PubMedCrossRefGoogle Scholar
  5. 5.
    Braak H, Braak E (1991) Neuropathological stageing of Alzheimer-related changes. Acta Neuropathol 82: 239–259PubMedCrossRefGoogle Scholar
  6. 6.
    Goedert M (1993) Tau protein and the neurofibrillary pathology of Alzheimer’s disease. Trends Neurosci 16: 460–465PubMedCrossRefGoogle Scholar
  7. 7.
    Selkoe DJ (1994) Normal and abnormal biology of the β-amyloid precursor protein. Ann Rev Neurosci 17: 489–517PubMedCrossRefGoogle Scholar
  8. 8.
    Selkoe DJ (1989) Aging, amyloid, and Alzheimer’s disease. N Engl J Med 320: 1484–1487PubMedCrossRefGoogle Scholar
  9. 9.
    Tagliavini F, Giaccone G, Frangione B, Bugiani O (1988) Preamyloid deposits in the cerebral cortex of patients with Alzheimer’s disease and non demented individuals. Neurosci Lett 93: 191–196PubMedCrossRefGoogle Scholar
  10. 10.
    Li Y-T, Woodruff-Pack DS, Trojanowski JQ (1994) Amyloid plaques in cerebellar cortex and the integrity of Purkinje cell dendrites. Neurobiol Aging 15: 1–9PubMedCrossRefGoogle Scholar
  11. 11.
    Joachim CJ, Mori H, Selkoe DJ (1989) Amyloid β-protein deposition in tissues other than brain in Alzheimer’s disease. Nature 341: 226–230PubMedCrossRefGoogle Scholar
  12. 12.
    Mann DMA (1994) Pathological correlates of dementia in Alzheimer’s disease. Neurobiol Aging 15: 357–360PubMedCrossRefGoogle Scholar
  13. 13.
    Schmidt ML, Lee VM, Forman M, Chiu TS, Trojanowski JQ (1997) Monoclonal antibodies to a 100-kd protein reveal abundant Aβ-negative plaques throughout gray matter of Alzheimer’s disease brains. Am J Pathol 151: 69–80PubMedGoogle Scholar
  14. 14.
    Davies P, Verth AH (1978) Regional distribution of muscarinic acetylcholine receptors in normal and Alzheimer’s type dementia brains. Brain Res 138: 385–392CrossRefGoogle Scholar
  15. 15.
    Shimohama S, Taniguchi T, Fujiwara M, Kameyama M (1986) Changes in nicotinic and muscarinic cholinergic receptors in Alzheimer-type dementia. J Neurochem 46: 288–293PubMedCrossRefGoogle Scholar
  16. 16.
    Horsburg K, Saitoh T (1994) Altered signal transduction in Alzheimer disease. In: Terry RD, Katzman R, Bick KL (eds) Alzheimer disease. Raven, New York, pp 387–404Google Scholar
  17. 17.
    Poirier J, Delisle MC, Quirion R, Aubert I, Farlow M, Lahiri D, Hui S, Bertrand P, Nalbantoglu J, Gilfix BM, et al (1995) Apolipoprotein E4 allele as a predictor of cholinergic deficits and treatment outcome in Alzheimer disease. Proc Natl Acad Sci USA 92: 12260–12264PubMedCrossRefGoogle Scholar
  18. 18.
    Cowburn RF, Fowler CJ, O’Neill C (1996) Neurotransmitters, signal transduction and second-messengers in Alzheimer’s disease. Acta Neurol Scand Suppl 165: 25–32PubMedCrossRefGoogle Scholar
  19. 19.
    Cowburn RF, Fowler CJ, O’Neill C (1996) Neurotransmitter receptor/G-protein mediated signal transduction in Alzheimer’s disease brain. Neurodegeneration 5: 483–488PubMedCrossRefGoogle Scholar
  20. 20.
    Fowler CJ, Garlind A, O’Neill C, Cowburn RF (1996) Receptor-effector coupling dysfunctions in Alzheimer’s disease. Ann N Y Acad Sci 786: 294–304PubMedCrossRefGoogle Scholar
  21. 21.
    Van Huyn T, Cole G, Katzman R, Huang K-P, Saitoh T (1989) Reduced protein kinase C immunoreactivity and altered protein phosphorylation in Alzheimer’s disease fibroblasts. Arch Neurol 46: 1195–1199CrossRefGoogle Scholar
  22. 22.
    Bruel A, Cherqui G, Columelli S, Margelin D, Roudier M, Sinet PM, Prieur M, Perignon JL, Delabar J (1991) Reduced protein kinase C activity in sporadic Alzheimer’s disease fibroblasts. Neurosci Lett 133: 89–92PubMedCrossRefGoogle Scholar
  23. 23.
    Govoni S, Bergamaschi S, Racchi M, Battaini F, Binetti G, Bianchetti A, Trabucchi M (1993) Cytosol protein kinase C downregulation in fibroblasts from Alzheimer’s disease patients. Neurology 43: 2581–2586PubMedCrossRefGoogle Scholar
  24. 24.
    Bergamaschi S, Binetti G, Govoni S, Wetsel WC, Battaini F, Trabucchi M, Bianchetti A, Racchi M (1995) Defective phorbolester-stimulated secretion of β-amyloid precursor protein from Alzheimer’s disease fibroblasts. Neurosci Lett 201: 1–4PubMedCrossRefGoogle Scholar
  25. 25.
    Racchi M, Bergamaschi S, Govoni S, Wetsel WC, Bianchetti A, Binetti G, Battaini F, Trabucchi M (1994) Characterization and distribution of protein kinase C isoforms in human skin fibroblasts. Arch Biochem Biophys 314: 107–111PubMedCrossRefGoogle Scholar
  26. 26.
    Vestling M, Adem M, Lannfelt L, Cowburn RF (1995) Protein kinase C levels and activity in cultured skin fibroblasts from affected and non-affected members of the Swedish family with the amyloid precursor protein 670/671 mutation. Soc Neurosci Abs 21: 774.14Google Scholar
  27. 27.
    Huang HM, Gibson GE (1993) Altered β-adrenergic receptor stimulated cAMP formation in cultured skin fibroblasts from Alzheimer donors. J Biol Chem 268: 14616–14621PubMedGoogle Scholar
  28. 28.
    Vestling M, Adem A, Racchi M, Gibson GE, Lannfelt L, Cowburn RF (1997) Differential regulation of adenylyl cyclase in fibroblasts from sporadic and familial Alzheimer’s disease cases with PS1 and APP mutations. Neuroreport 8: 2031–2035PubMedCrossRefGoogle Scholar
  29. 29.
    Huang HM, Lin TA, Sun GY, Gibson GE (1995) Increased inositol 1,4,5-trisphosphate accumulation correlates with an up-regulation of bradykinin receptors in Alzheimer’s disease. J Neurochem 64: 761–766PubMedCrossRefGoogle Scholar
  30. 30.
    Glenner GC, Wong CW (1984) Alzheimer’s disease: initial report of the purification and characterization of a novel cerebrovascular amyloid protein. Biochem Biophys Res Commun 120: 885–890PubMedCrossRefGoogle Scholar
  31. 31.
    Kang J, Lemaire HG, Unterbeck A, et al (1987) The precursor of Alzheimer’s disease amyloid A4 protein resembles a cell-surface receptor. Nature 325: 733–736PubMedCrossRefGoogle Scholar
  32. 32.
    Ponte P, Gonzalez-De Whitt P, Schilling J, et al (1988) A new A4 amyloid mRNA contains a domain homologous to serine proteinase inhibitors. Nature 331: 525–527PubMedCrossRefGoogle Scholar
  33. 33.
    Tanzi RE, McClatchey AI, Lamperti ED, et al (1988) Protease inhibitor domain encoding by an amyloid protein precursor mRNA associated with Alzheimer disease. Nature 331: 528–530PubMedCrossRefGoogle Scholar
  34. 34.
    Kitaguchi N, Takahashi Y, Tokushima Y, et al (1988) Novel precursor of Alzheimer’s disease amyloid protein shows protease inhibitory activity. Nature 331: 530–532PubMedCrossRefGoogle Scholar
  35. 35.
    Goldgaber D, Lerman MI, McBride OW, Saffiotti U, Gajdusek C (1987) Characterization and chromosomal localization of a cDNA encoding brain amyloid of Alzheimer disease. Science 235: 877–880PubMedCrossRefGoogle Scholar
  36. 36.
    Schellenberg GD (1995) Genetic dissection of Alzheimer disease, a heterogeneous disorder. Proc Natl Acad Sci USA 92: 8552–8559PubMedCrossRefGoogle Scholar
  37. 37.
    Iversen LL, Mortishire-Smith RJ, Pollack SJ, Shearman MS (1995) The toxicity in vitro of beta-amyloid protein. Biochem J 311: 1–16PubMedGoogle Scholar
  38. 38.
    Sherrington R, Rogaev El, Liang Y, et al (1995) Cloning of a gene bearing missense mutations in early-onset familial Alzheimer’s disease. Nature 375: 754–760PubMedCrossRefGoogle Scholar
  39. 39.
    Bird TD, Lampe TH, Nemens EJ, et al (1988) Familial Alzheimer’s disease in American descendants of the Volga-Germans: probable founder effect. Ann Neurol 23: 25–31PubMedCrossRefGoogle Scholar
  40. 40.
    Rogaev El, Sherrignton R, Rogaeva EA, et al (1995) Familial Alzheimer’s disease in kindreds with missense mutations in a gene on chromosome 1 related to the Alzheimer’s disease type 3 gene. Nature 376: 775–778PubMedCrossRefGoogle Scholar
  41. 41.
    Levy-Lahad E, Wasco W, Poorkaj P, et al (1995) Candidate gene for the chromosome 1 familial Alzheimer’s disease locus. Science 269: 973–977PubMedCrossRefGoogle Scholar
  42. 42.
    Levitan D, Greenwald I (1995) Facilitation of lin-12-mediated signalling by sel-12, a Caenorhabditis elegans S182 Alzheimer’s disease gene. Nature 377: 351–354PubMedCrossRefGoogle Scholar
  43. 43.
    Wolozin B, Iwasaki K, Vito P, Ganjei JK, Lacana E, Sunderland T, Zhao B, Kusiak JW, Wasco W, D’Adamio L (1996) Participation of presenilin 2 in apoptosis: enhanced basal activity conferred by an Alzheimer mutation. Science 274: 1710–1713PubMedCrossRefGoogle Scholar
  44. 44.
    Pericak-Vance MA, Bebout JL, Gaskell PC jr, et al (1991) Linkage studies in familial Alzheimer’s disease — evidence for chromosome 19 linkage. Am J Hum Genet 48: 1034–1050PubMedGoogle Scholar
  45. 45.
    Saunders AM, Strittmatter WJ, Schmechel D, et al (1993) Association of apolipoprotein E allele epsilon 4 with late-onset familial and sporadic Alzheimer’s disease. Neurology 43: 1467–1472PubMedCrossRefGoogle Scholar
  46. 46.
    Frisoni GB, Govoni S, Geroldi C, Bianchetti A, Calabresi L, Franceschini G, Trabucchi M (1995) Gene dose of the e4 allele of Apolipoprotein E and disease progression in sporadic late onset Alzheimer’s disease. Ann Neurol 37: 596–604PubMedCrossRefGoogle Scholar
  47. 47.
    Payami H, Schelllenberg GD, Zareparsi Z, Kaye J, Sexton GJ, Head MA, Matsuyama SS, Jarvik LF, Miller B, McManus DQ, Bird TD, Katzman R, Heston L, Nornan D, Small GW (1997) Evidence for association of HLA-A2 allele with onset age of Alzheimer’s disease. Neurology 49: 512–518PubMedCrossRefGoogle Scholar
  48. 48.
    Pericak-Vance MA, Bass MP, Yamaoka LH, Gaskell PC, Scott WK, Terwedow HA, Menold MM, Conneally PM, Small GW, Vance JM, Saunders AM, Roses AD, Haines JL (1997) Complete genomic screen in late-onset familial Alzheimer disease. Evidence for a new locus on chromosome 12. JAMA 278: 1237–1241PubMedCrossRefGoogle Scholar
  49. 49.
    Sisodia SS (1992) Beta-amyloid precursor protein cleavage by a membrane bound protease. Proc Natl Acad Sci USA 89: 6075–6079PubMedCrossRefGoogle Scholar
  50. 50.
    Shoji M, Golde TE, Ghiso J, Cheung TT, Estus S, Shaffer LM, Cai X-D, McKay DM, Tintner R, Frangione B, Younkin SG (1992) Production of the Alzheimer amyloid b protein by normal proteolytic processing. Science 258: 126–129PubMedCrossRefGoogle Scholar
  51. 51.
    Checler F (1995) Processing of the β-amyloid precursor protein and its regulation in Alzheimer’s disease. J Neurochem 65: 1431–1444PubMedCrossRefGoogle Scholar
  52. 52.
    Citron M, Vigo-Pelfrey C, Teplow DB, Miller C, Schenk D, Johnston J, Winblad B, Venizelos N, Lanfelt L, Selkoe DJ (1994) Excessive production of amyloid b-protein by peripheral cells of symptomatic and presymptomatic patients carrying the Swedish familial Alzheimer disease mutation. Proc Natl Acad Sci USA 91: 11993–11997PubMedCrossRefGoogle Scholar
  53. 53.
    Scheuner D, Eckman C, Jensen M, Song X, Citron M, Suzuki N, Bird TD, Hardy J, Hutton M, Kukull W, Larson E, Levy-Lahad E, Vitanen M, Peskind E, Poorkaj P, Schellenberg G, Tanzi R, Wasco, W, Lannfelt L, Selkoe D, Younkin S (1996) Secreted amyloid bprotein similar to that in the senile plaques of Alzheimer’s disease is increased in vivo by the presenilin 1 and 2 and APP mutations linked to familial Alzheimer’s disease. Nat Med 2: 864–870PubMedCrossRefGoogle Scholar
  54. 54.
    Mattson MP, Barger SW, Cheng B, Lieberburg I, Smith-Swintosky VL, Rydel RE (1993) β-amyloid precursor protein metabolites and loss of neuronal Ca2+ homeostasis in Alzheimer’s disease. Trends Neurosci 16: 409–414PubMedCrossRefGoogle Scholar
  55. 55.
    Mattson MP, Cheng B, Davis D, Bryant K, Lieberburg I, Rydell RE (1992) Beta amyloid peptides destabilize calcium homeostasis and render human cortical neurons vulnerable to excitotoxicity. J Neurosci 12: 376–389PubMedGoogle Scholar
  56. 56.
    Govoni S, Gasparini L, Racchi M, Trabucchi M (1996) Peripheral cells as an investigational tool for Alzheimer’s disease. Life Sci 59: 461–468PubMedCrossRefGoogle Scholar
  57. 57.
    Gibson G, Martins R, Blass J, Gandy S (1996) Altered oxidation and signal transduction systems in fibroblasts from Alzheimer patients. Life Sci 59: 477–489PubMedCrossRefGoogle Scholar
  58. 58.
    Parker WD, Filley CM, Parks JK (1990) Cytochrome c oxidase deficiency in Alzheimer’s disease. Neurology 40: 1302–1303PubMedCrossRefGoogle Scholar
  59. 59.
    Curti D, Rognoni F, Gasparini L, Cattaneo A, Paolillo M, Racchi M, Zani L, Bianchetti A, Trabucchi M, Bergamaschi S, Govoni S (1997) Oxidative metabolism in cultured fibroblasts derived from sporadic Alzheimer’s disease (AD) patients. Neurosci Lett 235: 1–4CrossRefGoogle Scholar
  60. 60.
    Davis RE, Miller S, Herrnstadt C, Ghosh SS, Fahy E, Shinobu LA, Galasko D, Thal LJ, Beal MF, Howell N, Parker DW (1997) Mutations in mitochondrial cytochrome c oxidase genes segregate with late onset Alzheimer’s disease. Proc Natl Acad Sci USA 94: 4526–4531PubMedCrossRefGoogle Scholar
  61. 61.
    Hirashima N, Etcheberrigaray R, Bergamaschi S, Racchi M, Battaini F, Binetti G, Govoni S, Alkon DL (1996) Calcium responses in human fibroblasts: a diagnostic molecular profile for Alzheimer’s disease. Neurobiol Aging 17: 549–555PubMedCrossRefGoogle Scholar
  62. 62.
    Etcheberrigaray R, Ito E, Oka K, Tofel-Grehl B, Gibson GE, Alkon DL (1993) Potassium channel dysfunction in fibroblasts identifies patients with Alzheimer disease. Proc Natl Acad Sci USA 90: 8209–8213PubMedCrossRefGoogle Scholar
  63. 63.
    Ito E, Oka K, Etcheberrigaray R, Nelson TJ, McPhie DL, Tofel-Grehl B, Gibson GE, Alkon DL (1994) Internal Ca2+ mobilization is altered in fibroblasts from patients with Alzheimer disease. Proc Natl Acad Sci USA 91: 534–538PubMedCrossRefGoogle Scholar
  64. 64.
    Di Luca M, Pastorino L, Cattabeni F, Zanardi R, Racagni G, Smeraldi E, Perez J (1996) Abnormal pattern of platelet APP isoforms in Alzheimer’s disease and Down syndrome. Arch Neurol 53: 1162–1166PubMedCrossRefGoogle Scholar
  65. 65.
    Seubert P, Vigo-Pelfrey C, Esch F, Lee M, Dovey H, Davis D, Sinha S, Schlossmacher M, Whaley J, Swindlehurst C, et al (1992) Isolation and quantification of soluble Alzheimer’s beta-peptide from biological fluids. Nature 359: 325–327PubMedCrossRefGoogle Scholar
  66. 66.
    Gasparini L, Racchi M, Binetti G, Trabucchi M, Solerte SB, Alkon D, Etcheberrigaray R, Gibson G, Blass J, Paoletti R, Govoni S (1998) Peripheral markers in testing pathophysiological hypotheses and diagnosing Alzheimer’s disease. FASEB J 12: 17–34PubMedGoogle Scholar
  67. 67.
    Iwatsubo T, Odaka A, Suzuki N, Mizusawa H, Nukina N, Ihara Y (1994) Visualization of Aβ42(43) and Aβ40 in senile plaques with end-specific monoclonale: evidence that an initially deposited species is Aβ42(43). Neuron 13: 45–52PubMedCrossRefGoogle Scholar
  68. 68.
    Jensen M, Song XH, Suzuki N, Lanfelt L, Younkin SG (1995) The βAPP670/671 Alzheimer mutation (Swedish) increases plasma amyloid b protein concentration. Soc Neurosci Abs 21: 1501Google Scholar
  69. 69.
    Younkin LH, Eckman CB, Yager D, Graff-Rafford N, Younkin SG (1996) Analysis of plasma Aβ concentration in sporadic AD patients and non-demented subjects of all ages. Neurobiol Aging 17[4S]: S167CrossRefGoogle Scholar
  70. 70.
    Arai H, Terajima M, Miura M, Higuchi S, Muramatsu T, Machida N, Sciki H, Takase S, Clark CM, Lee VM-Y, Trojanowski JQ, Sasaki H (1995) Tau in cerebrospinal fluid: a potential diagnostic marker in Alzheimer’s disease. Ann Neurol 38: 649–652PubMedCrossRefGoogle Scholar
  71. 71.
    Kennard ML, Feldman H, Yamada T, Jefferies WA (1996) Serum levels of the iron binding protein p97 are elevated in Alzheimer’s disease. Nat Med 2: 1230–1235PubMedCrossRefGoogle Scholar
  72. 72.
    O’Brien MD (1994) How does cerebrovascular disease cause dementia? Dementia 5: 126–133Google Scholar
  73. 73.
    Brun A (1994) Pathology and pathophysiology of cerebrovascular dementia: pure subgroups of obstructive and hypoperfusive etiology. Dementia 5: 145–147PubMedGoogle Scholar
  74. 74.
    Zhang WW, Badonic T, Hooh A, Jiang MH, Ma KC, Nie JX, Olsson Y, Sourander P (1994) Structural and vasoactive factors influencing Intracerebral arterioles in cases of vascular dementia and other cerebroavscular disease: a review. Dementia 5: 153–162PubMedGoogle Scholar
  75. 75.
    Pasquier F, Leys D (1997) Why are stroke patients prone to develop dementia? J Neurol 244: 135–142PubMedCrossRefGoogle Scholar
  76. 76.
    Gottfries CG, Blennow K, Karlsson I, Wallin A (1994) The neurochemistry of vascular dementia. Dementia 5: 163–167PubMedGoogle Scholar
  77. 77.
    Tournier-Lasserve E, Joutel A, Melki J, Weissenbach J, Lathrop GM, Chabriat H, Mas JL, Cabanis EA, Baudrimont M, Maciazek J, et al (1993) Cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy maps to chromosome 19ql2. Nat Genet 3: 256–259PubMedCrossRefGoogle Scholar
  78. 78.
    Joutel A, Corpechot C, Ducros A, Vahedi K, Chabriat H, Mouton P, Alamowitch S, Domenga V, Cecillion M, Marechal E, Maciazek J, Vayssiere C, Cruaud C, Cabanis EA, Ruchoux MM, Weissenbach J, Bach JF, Bousser MG, Tournier-Lasserve E (1996) Notch3 mutations in CADASIL, a hereditary adult-onset condition causing stroke and dementia. Nature 383: 707–710PubMedCrossRefGoogle Scholar
  79. 79.
    Baudrimont M, Dubas F, Joutel A, Tournier-Lasserve E, Bousser MG (1993) Autosomal dominant leukoencephalopathy and subcortical ischemic stroke. A clinicopathological study. Stroke 24: 122–125PubMedCrossRefGoogle Scholar
  80. 80.
    Frisoni GB, Calabresi L, Geroldi C, Bianchetti A, D’Acquarica AL, Govoni S, Sirtori CR, Trabucchi M, Franceschini G (1994) Apolipoprotein E epsilon 4 allele in Alzheimer’s disease and vascular dementia. Dementia 5: 240–242PubMedGoogle Scholar
  81. 81.
    The Lund and Manchester Groups (1994) Clinical and neuropathological criteria for frontotemporal dementia. J Neurol Neurosurg Psychiatry 57: 416–418CrossRefGoogle Scholar
  82. 82.
    Foster NL, Wilhelmsen K, Sima AAF, Jones MZ, D’Amato CJ, Gilman S, and Conference Participants (1997) Frontotemporal dementia and Parkinsonism linked to chromosome 17: a consensus conference. Ann Neurol 41: 706–715PubMedCrossRefGoogle Scholar
  83. 83.
    Von Sattel JP, Binetti G, Welley LM (1976) Pick disease from molecular mechanism of dementia. In: Wasco W, Tanzi R (eds) Molecular basis of dementia. Humana, Totowa NJ, pp 253–269Google Scholar
  84. 84.
    Kosaka K, Iseki E (1996) Dementia with Lewy bodies. Curr Opin Neurol 9: 971–975CrossRefGoogle Scholar
  85. 85.
    Kalra S, Bergeron C, Lang AE (1996) Lewy body disease and dementia. A review. Arch Intern Med 156: 487–493PubMedCrossRefGoogle Scholar
  86. 86.
    Dickson DW, Wu E, Crystal HA, Mattiace LA, Yen SHC, Davies P (1992) Alzheimer’s disease and age related pathology in difuse Lewy body disease. In: Boller F, Forette F, Khachaturian Z, Poncet M, Christen Y (eds) Heterogeneity of Alzheimer’s disease. Springer, Berlin Heidelberg New York, pp 168–186CrossRefGoogle Scholar
  87. 87.
    Liberini P, Valerio A, Memo M, Spano P (1996) Lewy body dementia and responsiveness to Cholinesterase inhibitors: a paradigm for heterogeneity of Alzheimer’s disease? Trends Pharmacol Sci 17: 155–160PubMedCrossRefGoogle Scholar
  88. 88.
    Katzman R, Galasko D, Saitoh T, Tal LJ, Hansen L (1995) Genetic evidence that the Lewy body variant is indeed a phenotypic variant of Alzheimer’s disease. Brain Cogn 28: 259–265PubMedCrossRefGoogle Scholar
  89. 89.
    Goldfarb LG, Brown P (1995) The transmissible spongiform encephalopathies. Annu Rev Med 46: 57–65PubMedCrossRefGoogle Scholar
  90. 90.
    Parchi P, Gambetti P (1995) Human prion diseases. Curr Opin Neurol 8: 286–293PubMedCrossRefGoogle Scholar
  91. 91.
    Prusiner SB (1996) Molecular biology and pathogenesis of prion diseases. Trends in Biochem Sci 21: 482–487CrossRefGoogle Scholar
  92. 92.
    Zerr I, Bodemer M, Otto M, Poser S, Windl O, Kretzschmar HA, Gefeller O, Weber T (1996) Diagnosis of Creutzfeldt-Jakob disease by two-dimensional gel electrophoresis of cerebrospinal fluid. Lancet 348: 846–849PubMedCrossRefGoogle Scholar
  93. 93.
    Lee MK, Borchelt DR, Wong PC, Sisodia SS, Price DL (1996) Transgenic models of neurodegenerative diseases. Curr Opin Neurobiol 6: 651–660PubMedCrossRefGoogle Scholar
  94. 94.
    Cole GM, Frautschy SA (1997) Animal models for Alzheimer’s disease. Alzheimer’s Dis Rev 2: 33–41Google Scholar
  95. 95.
    Games D, Adams D, Alessandrini R, Barbour R, Berthelette P, Blackwell C, Carr T, Clemens J, Donaldson T, Gillespie F, Guido T, Hagopian S, Johnson-Wood K, Khan K, Lee M, Leibowitz P, Lieberburg I, Little S, Masliah E, McConlogue L, Montoya-Zavala M, Mucke L, Paganini L, Penniman E (1995) Alzheimer-type neuropathology in transgenic mice overexpressing V717F beta-amyloid precursor protein. Nature 373: 523–527PubMedCrossRefGoogle Scholar
  96. 96.
    Hsiao K, Chapman P, Nilsen D, Eckman C, Harigaya Y, Younkin S, Yang F, Cole G (1996) Correlative memory deficits, Aβ elevation and amyloid plaques in transgenic mice. Science 274: 99–102PubMedCrossRefGoogle Scholar
  97. 97.
    Hsiao K, Scott M, Foster D, Groth DF, Dearmond FJ, Prusiner SB (1990) Spontaneous neurodegeneration in transgenic mice with mutant prion protein. Science 250: 1587–1590PubMedCrossRefGoogle Scholar
  98. 98.
    Telling GC, Scott M, Mastrianni J, Gabizon R, Torchia M, Cohen FE, Dearmond SJ, Prusiner SB (1995) Prion propagation in mice expressing human and chimeric PrP transgenes implicates interaction of cellular PrP with another protein. Cell 83: 79–90PubMedCrossRefGoogle Scholar
  99. 99.
    Forloni G (1996) Neurotoxicity of beta amyloid and prion peptides. Curr Opin Neurol 9: 492–500PubMedCrossRefGoogle Scholar
  100. 100.
    Forloni G, Angeretti N, Chiesa R, Monzani E, Salmona M, Bugiani O, Tagliavini F (1993) Neurotoxicity of a prion protein fragment. Nature 362: 543–546PubMedCrossRefGoogle Scholar
  101. 101.
    Yankner BA (1996) Mechanisms of neuronal degeneration in Alzheimer’s disease. Neuron 16: 921–932PubMedCrossRefGoogle Scholar
  102. 102.
    Behl C, Davis JB, Klier FG, Shubert D (1994) Amyloid beta peptide induces necrosis rather than apoptosis. Brain Res 645: 253–264PubMedCrossRefGoogle Scholar

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© Springer-Verlag Italia 1999

Authors and Affiliations

  • M. Racchi
  • S. Govoni

There are no affiliations available

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