Skip to main content
Brain Pathology logoLink to Brain Pathology
. 2006 Apr 5;16(1):71–79. doi: 10.1111/j.1750-3639.2006.tb00563.x

Genetic Alterations of the BRI2 gene: Familial British and Danish Dementias

Ghiso J 1,2,, Rostagno A 1, Tomidokoro Y 1, Lashley T 3, Bojsen‐Møller M 4, Braendgaard H 5, Plant G 6, Holton J 3, Lal R 7, Revesz T 3, Frangione B 1,2
PMCID: PMC8095812  PMID: 16612984

Abstract

Classic arguments sustaining the importance of amyloid in the pathogenesis of dementia are usually centered on amyloid β (Aβ) and its role in neuronal loss characteristic of Alzheimer disease, the most common form of human cerebral amyloidosis. Two non‐Aβ cerebral amyloidoses, familial British and Danish dementias, share many aspects of Alzheimer disease, including the presence of neurofibrillary tangles, parenchymal pre‐amyloid and amyloid deposits, cerebral amyloid angiopathy, and a widespread inflammatory response. Both early‐onset conditions are linked to specific mutations in the BRI2 gene, causing the generation of longer‐than‐normal protein products and the release of 2 de novo created peptides ABri and ADan, the main components of amyloid fibrils in these inherited dementias. Although the molecular mechanisms and signal transduction pathways elicited by the amyloid deposits and their relation to cognitive impairment remain to be clarified, new evidence indicates that, independent of the differences in their primary structures, Aβ, ABri, and ADan subunits are able to form morphologically compatible ion‐channel‐like structures and elicit single ion‐channel currents in reconstituted lipid membranes. These findings reaffirm the notion that non‐ Aβ amyloidosis constitute suitable alternative models to study the role of amyloid deposition in the mechanism of neuronal cell death.

References

  • 1. Akiyama H, Barger S, Barnum S, Bradt B, Bauer J, Cole GM, Cooper NR, Eikelenboom P, Emmer‐ling MR, Fiebich BL, et al (2000) Inflammation and Alzheimer's Disease. Neurobiol Aging 21:383–421. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 2. Akiyama H, Kondo H, Arai T, Ikeda K, Kato M, Iseki E, Schwab C, McGeer PL (2004) Expression of BRI, the normal precursor of the amyloid protein of familial British dementia, in human brain. Acta Neuropathol 107:53–58. [DOI] [PubMed] [Google Scholar]
  • 3. Arispe N (2004) Architecture of the Alzheimers AβP ion channel pore. J Membrane Biol 197:33–48. [DOI] [PubMed] [Google Scholar]
  • 4. Behl C, Davis JB, Klier FG, Schubert D (1994) Amyloid b peptide induces necrosis rather than apoptosis. Brain Res 645:253–264. [DOI] [PubMed] [Google Scholar]
  • 5. Bek T (2000) Ocular changes in heredootoophtalmo‐encephalopathy. British J Ophtalmol 84: 1298–1302. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 6. Busby WH, Quackenbush GE, Humm J, Young‐blood WW, Kizer JS (1987) n enzyme that converts glutaminyl‐peptides into pyroglutamyl‐peptides. J BiolChem 262: 8532–8536. [PubMed] [Google Scholar]
  • 7. Choi SC, Kim J, Kim TH, Cho SY, Park SS, Kim KD, Lee SH (2001) Cloning and characterization of a type II integral transmembrane protein gene, Itm2c, that is highly expressed in the mouse brain. Mol Cells 12:391–397. [PubMed] [Google Scholar]
  • 8. Choi SI, Vidal R, Frangione B, Levy E (2004) Axo‐nal transport of British and Danish amyloid peptides via secretory vesicles. FASEBJ 18:373–375. [DOI] [PubMed] [Google Scholar]
  • 9. Creagh EM, Martin SJ (2001) Caspases: cellular demolition experts. Biochem Soc Trans 29:696–702. [DOI] [PubMed] [Google Scholar]
  • 10. Davis JB, Cribbs DH, Cotman CW, van Nostrand WE (1999) Pathogenic amyloid beta‐protein induces apoptosis in cultured human cerebrovascular smooth muscle. Amyloid: Intl J Exp Clin Invest 6:157–164. [DOI] [PubMed] [Google Scholar]
  • 11. Deleersnijder W, Hong G, Cortvrindt R, Poirier C, Tyzanowski P, Pittois K, van Marck E, Merregaert J (1996) Isolation of markers for chondroosteogenic differentiation using cDNA library substraction. J Biol Chem 271: 19475–19482. [DOI] [PubMed] [Google Scholar]
  • 12. Denecker G, Vercammen D, Declercq W, Vandenabeele P (2001) Apoptotic and necrotic cell death induced by death domain receptors. Cell Mol Life Sci 58:356–370. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 13. Emmerling MR, Watson MD, Raby CA, Spiegel K (2000) The role of complement in Alzheimer's disease pathology. Biochim Byophys Acta 1502:158–171. [DOI] [PubMed] [Google Scholar]
  • 14. Fischer WH, Spiess J (1987) Identification of a mammalian glutaminyl cyclase converting glutaminyl into pyroglutamyl peptides. Proc NatlAcad SciUSA 84:3628–3632. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 15. Fleisher A, Ayllon V, Dumoutier L, Renauld JC, Rebollo A (2002) Proapoptotic activity of ITM2B(s), a BH3–only protein induced upon IL‐2 deprivation which interacts with Bcl‐2. Oncogene 21:3181–3189. [DOI] [PubMed] [Google Scholar]
  • 16. Fleisher A, Rebollo A (2004) Induction of p53–independent apoptosis by BH3‐only protein IT‐M2Bs. FEBS Lett 557:283–287. [DOI] [PubMed] [Google Scholar]
  • 17. Fotinopoulou A, Tsachaki M, Vlavaki M, Poulo‐poulos A, Rostagno A, Frangione B, Ghiso J, Efthimiopoulos S (2005) BRI2 interacts with amyloid precursor protein (APP) and regulates amyloid beta (Aβ) production. J Biol Chem 280: 30768–30772. [DOI] [PubMed] [Google Scholar]
  • 18. Ghiso J, Holton J, Miravalle L, Calero M, Lashley T, Vidal R, Houlden H, Wood N, Neubert TA, Rostagno A, et al (2001) Systemic amyloid deposits in Familial British Dementia. J Biol Chem 276:43909–43914. [DOI] [PubMed] [Google Scholar]
  • 19. Gibson G, Gunasekera N, Lee M, Lelyveld V, El‐Agnaf OMA, Wright A, Austen BM (2004) Oligomerization and neurotoxicity of the amyloid ADan peptide implicated in familial Danish dementia. J Neurochem 88:281–290. [DOI] [PubMed] [Google Scholar]
  • 20. Griffin WST, Sheng JG, Royston MC, Gentleman SM, McKenzie J, Graham DI, Roberts GW, Mrak RE (1998) Glial‐neuronal interactions in Alzheimer's disease: the potential role of a “cytokinecycle” in disease progression. Brain Pathol 8:65–72. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 21. Griffiths R, Mortimer T, Oppenheimer D, Spalding J (1982) Congophilic angiopathy of the brain: a clinical and pathological report on two siblings. J Neurol Neurosurg Psych 45:396–408. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 22. Haass C, Steiner H (2001) Protofibrils, the unifying toxic molecule of neurodegenerative disorders Nat Neurosci 4:859–860. [DOI] [PubMed] [Google Scholar]
  • 23. Hirakura Y, Lin M‐C, Kagan BL (1999) Alzheimers amyloid Aβ 1–42 channels: Effect of solvent, pH and Congo red. J Neurosci Res 57:458–466. 10440895 [Google Scholar]
  • 24. Holton J, Ghiso J, Lashley T, Ganguly M, Strand K, Rostagno A, Plant G, Frangione B, Revesz T (2002) Familial British Dementia (FBD): a cerebral amyloidosis with systemic amyloid deposition. Neuropathol Appl Neurobiol 28:148. [Google Scholar]
  • 25. Holton J, Ghiso J, Lashley T, Rostagno A, Guerin C, Gibb G, Houlden H, Ayling H, Martinian L, Anderton B, et al (2001) Regional distribution of fibrillar and non‐fibrillar ABri deposition and its association with neurofibrillary degeneration in Familial British Dementia. Am J Pathol 158:515–526. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 26. Holton J, Lashley T, Ghiso J, Braendgaard H, Vidal R, Guerin C, Gibb G, Hanger DP, Rostagno A, Anderton B, et al (2002) Familial Danish Dementia: a novel form of cerebral amyloidosis associated with deposition of both amyloid‐Dan and amyloid‐beta. J Neuropathol Exp Neurol 61:254–267. [DOI] [PubMed] [Google Scholar]
  • 27. Kagan BL, Azimov R, Azimova R (2004) Amyloid peptide channels. J Membrane Biol 202:1–10. [DOI] [PubMed] [Google Scholar]
  • 28. Kim S‐H, Creemers JW, Chu S, Thinakaran G, Sisodia SS (2002) Proteolytic processing of familial British dementia‐associated BRI variants: evidence for enhanced intracellular accumulation of amyloidogenic peptides. J Biol Chem 277:1872–1877. [DOI] [PubMed] [Google Scholar]
  • 29. Kim S‐H, Wang R, Gordon DJ, Bass J, Steiner D, Lynn DG, Thinakaran G, Meredith S, Sisodia SS (1999) Furin mediates enhanced production of fibrillogenic ABri peptides in familial British dementia. Nat Neurosci 2:984–988. [DOI] [PubMed] [Google Scholar]
  • 30. Kirchner J, Bevan MJ (1999) ITM2A is induced during thymocyte selection and T cell activation and causes downregulation of CD8 when overexpressed in CD4 (+)CD8(+) double positive thymocytes. J Exp Med 190:217–228. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 31. Klein WL, Krafft GA, Finch C (2001) Targeting small Ab oligomers: the solution to an Alzheimer's disease conundrum Trends Neurosci 24:219–224. [DOI] [PubMed] [Google Scholar]
  • 32. Koo EH, Sisodia SS, Archer DR, Martin LJ, Weidemann A, Beyreuther K, Fischer P, Masters CL, Price DL (1990) Precursor of amyloid protein in Alzheimer disease undergoes fast anterograde axonal transport. Proc Natl Acad Sci USA 87:1561–1565. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 33. Kuo YM, Emmerling MR, Vigo‐Pelfrey C, Kasunic TC, Kirkpatrick JB, Murdoch GH, Ball MJ, Roher AE (1996) Water‐soluble Abeta (N‐40, N‐42) oligomers in normal and Alzheimer disease brains. J Biol Chem 271:4077–4081. [DOI] [PubMed] [Google Scholar]
  • 34. Lambert MP, Barlow AK, Chromy BA, Edwards C, Freed R, Liosatos M, Morgan TE, Rozovsky I, Trommer B, Viola KL, et al (1998) Diffusible, nonfibrillar ligands derived from Aβ1–42 are potent central nervous system neurotoxins. Proc Natl Acad Sci USA 95:6448–6453. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 35. Lambert MP, Viola KL, Chromy BA, Chang L, Morgan TE, Yu J, Venton DL, Krafft GA, Finch C, Klein WL (2001) Vaccination with soluble A beta oligomers generates toxicity‐neutralizing antibodies. J Neurochem 79:595–605. [DOI] [PubMed] [Google Scholar]
  • 36. Lansbury PT (1999) Amyloid diseases: abnormal protein aggregation in neurodegeneration. Proc Natl Acad Sci USA 96:3342–3344. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 37. Lashley T, Holton JL, Verbeek MM, Rostagno A, Bojsen‐Møller M, David G, van Horseen J, Braendgaard H, Plant G, Frangione B, Ghiso J, Revesz T. (2006) Molecular chaperons, amyloid and pre‐amyloid lesions in the BRI2 gene‐related dementias: A morphological study. Neuropathol Appl Neurobiolin in press. [DOI] [PubMed] [Google Scholar]
  • 37. Lashuel HA, Hartley D, Petre BM, Walz T, Lansbury PTJ (2002) Neurodegenerative disease: amyloid pores from pathogenic mutations. Nature 418:291. [DOI] [PubMed] [Google Scholar]
  • 38. Latil A, Chene L, Mangin P, Fournier G, Berthon P, Cussenot O (2003) Extensive analysis of the 13q14 region in human prostate tumors: DNA analysis and quantitative expression of genes lying in the interval of deletion. Prostate 57:39–50. [DOI] [PubMed] [Google Scholar]
  • 39. Lin H, Bhatia R, Lal R (2001) Amyloid beta protein forms ion channels: implications for Alzheimer's disease pathophysiology. FASEB J 15:2433–2444. [DOI] [PubMed] [Google Scholar]
  • 40. Lin H, Zhu YJ, Lal R (1999) Amyloid beta protein (1–40) forms calcium‐permeable, Zn2+‐sen‐sitive channel in reconstituted lipid vesicles. Biochemistry 38:11189–11196. [DOI] [PubMed] [Google Scholar]
  • 41. Loo DT, Copani A, Pike CJ, Whittemore ER, Walencewicz AJ, Cotman CW (1993) Apoptosis is induced by b‐amyloid in cultured central nervous system neurons. Proc Natl Acad Sci USA 90:7951–7955. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 42. Love S, Duchen L (1982) Familial cerebellar ataxia with cerebrovascular amyloid. J Neurol Neurosurg Psych 45:271–273. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 43. Lue L‐F, Kuo Y‐M, Roher A, Brachova L, Shen Y, Sue L, Beach T, Kurth JH, Rydel R, Rogers J (1999) Soluble amyloid beta peptide concentration as a predictor of synaptic change in Alzheimer's disease. Am J Pathol 155:853–862. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 44. Mao M, Fu G, Wu JS, Zhang QH, Zhou J, Kan LX, Huang QH, He KL, Gu BW, Han ZG, et al (1998) Identification of genes expressed in human CD34(+) hematopoietic stem/progenitor cells by expressed sequence tags and efficient full‐length cDNA cloning. Proc Natl Acad Sci USA 95:8175–8180. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 45. Matsuda S, Giliberto L, Matsuda Y, Davies P, McGowan E, Pickford F, Ghiso J, Frangione B, D'Adamio L (2005) The familial dementia BRI2 gene binds the Alzheimer's gene amyloid‐beta precursor protein and inhibits amyloid‐beta production. J Biol Chem 280:28912–28916. [DOI] [PubMed] [Google Scholar]
  • 46. Mattson MP (2000) Apoptosis in neurodegenerative disorders. Nat Rev Molec Cell Biol 1:120–129. [DOI] [PubMed] [Google Scholar]
  • 47. McLean CA, Cherny RA, Fraser FW, Fuller SJ, Smith MJ, Beyreuther K, Bush AI, Masters CL (1999) Soluble pool of A beta amyloid as a determinant of severity of neurodegeneration in Alzheimer's disease. Ann Neurol 46:860–866. [DOI] [PubMed] [Google Scholar]
  • 48. Mead S, James Galton, M , Revesz T, Doshi RB, Harwood G, Pan EL, Ghiso J, Frangione B, Plant G (2000) Familial British dementia with amyloid angiopathy: Early clinical, neuropsychological and imaging findings. Brain 123:975–986. [DOI] [PubMed] [Google Scholar]
  • 49. Miravalle L, Tokuda T, Chiarle R, Giaccone G, Bugiani O, Tagliavini F, Frangione B, Ghiso J (2000) Substitution at codon 22 of Alzheimer's Aβ peptide induce diverse conformational changes and apoptotic effects in human cerebral endothelial cells. J Biol Chem 275:27110–27116. [DOI] [PubMed] [Google Scholar]
  • 50. Molloy SS, Anderson ED, Jean F, Thomas G (1999) By‐cycling the furin pathway: from TGN localization to pathogen activation and embryo‐genesis. Trends Cell Biol 9:28–35. [DOI] [PubMed] [Google Scholar]
  • 51. Mori, H . Takio, K . Ogawara, M , Selkoe D (1992) Mass spectromety of purified amyloid beta protein in Alzheimer's disease. J Biol Chem 267:17082–17086. [PubMed] [Google Scholar]
  • 52. Movsesyan VA, Stoica BA, Faden AI (2004) MGLuR5 activation reduces ?‐amyloid‐induced ell death in primary neuronal cultures and attenuates translocation of cytochrome c and apoptosis‐inducing factor. J Neurochem 89:1528–1536. [DOI] [PubMed] [Google Scholar]
  • 53. Nupponen NN, Hyytinen ER, Kallioniemi AH, Visakorpi T (1998) Genetic alterations in prostate cancer cell lines detected by comparative, genomic hybridization. Cancer Genet Cytogenet 101:53–57. [DOI] [PubMed] [Google Scholar]
  • 54. Oda, T . Wals, P . Osterburg, HH , Johnson SA, Pasinetti GM, Morgan TE, Rozovsky I, Stine WBJ, Snyder SW, Holzman TF, et al (1995) Clusterin (apoJ) alters the aggregation of amyloid beta‐peptide (A beta 1–42) and forms slowly sedimenting A beta complexes that cause oxidative stress. Exp Neurol 136:22–31. [DOI] [PubMed] [Google Scholar]
  • 55. Pittois K, Deleersnijder W, Merregaert J (1998) cDNA sequence analysis, chromosomal assignment and expression pattern of the gene coding for integral membrane protein 2B. Gene 217:141–149. [DOI] [PubMed] [Google Scholar]
  • 56. Pittois K, Wauters J, Bossuyt P, Deleersnijder W, Merregaert J (1999) Genomic organization and chromosomal localization of the Itm2a gene. Mamm Genome 10:54–56. [DOI] [PubMed] [Google Scholar]
  • 57. Plant G, Esiri MM (1997) Familial cerebral amyloid angiopathies. In: The neuropathology of dementia, Esiri, JH Morris (eds). Cambridge University Press: Cambridge pp. 260–276. [Google Scholar]
  • 58. Plant G, Revesz, T . Barnard, R , Harding A, Gautier‐Smith P (1990) Familial cerebral amyloid angiopathy with nonneuritic plaque formation. Brain 113:721–747. [DOI] [PubMed] [Google Scholar]
  • 59. Quist A, Doudevski I, Lin H, Azimova D, Ng D, Frangione B, Kagan B, Ghiso J, Lal R (2005) Amyloids form membrane pores: a common structural link for protein‐misfolding disease. Proc Natl Acad Sci USA 102:10427–10432. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 60. Revesz T, Ghiso J, Lashley T, Plant G, Rostagno A, Frangione B, Holton J (2003) Cerebral amyloid angiopathies: a pathologic, biochemical, and genetic view. J Neuropathol Exp Neurol 62:885–898. [DOI] [PubMed] [Google Scholar]
  • 61. Revesz T, Holton J, Lashley T, Plant G, Rostagno A, Ghiso J, Frangione B. (2002) Sporadic and familial cerebral amyloid angiopathies. Brain Pathol 12:343–357. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 62. Revesz T, Holton JL, Doshi B, Anderton BH, Scaravilli F, Plant G (1999) Cytoskeletal pathology in familial cerebral amyloid angiopathy (British type) with non‐neuritic amyloid plaque formation. Acta Neuropathol 97:170–176. [DOI] [PubMed] [Google Scholar]
  • 63. Rissoan MC, Duhen T, Bridon JM, Bendriss‐Vermare N, de Peronne CSV, Briere F, Bates EE (2002) Substractive hybridization reveals the expression of immunoglobulin‐like transcript 7, Eph‐B1, granzyme B, and 3 novel transcripts in human plasmacytoid dendritic cells. Blood 100:3295–3303. [DOI] [PubMed] [Google Scholar]
  • 64. Rogers J, Cooper NR, Webster S, Schultz J, Mc‐Geer PL, Styren SD, Civin WH, Brachova L, Bradt B, Ward P, et al (1992) Complement activation by b‐amyloid in Alzheimer's disease. Proc Natl Acad Sci US A 89:10016–10020. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 65. Roher AE, Chaney MO, Kuo YM, Webster SD, Stine WB, Haverkamp LJ, Woods AS, Cotter RJ, Tuohy JM, Krafft GA, et al (1996) Morphology and toxicity of Abeta‐(1–42) dimer derived from neuritic and vascular amyloid deposits of Alzheimer's disease. J Biol Chem 271:20631–20635. [DOI] [PubMed] [Google Scholar]
  • 66. Rostagno A, Revesz T, Lashley T, Tomidokoro Y, Magnotti L, Braendgaard H, Bojsen‐Moller M, Holton J, Frangione B, Ghiso J (2003) Complement activation in Chromosome 13 dementias: Similarities with Alzheimer's Disease. J Biol Chem 277:49782–49790. [DOI] [PubMed] [Google Scholar]
  • 67. Rostagno A, Tomidokoro Y, Lashley T, Ng D, Plant G, Holton J, Frangione B, Revesz T, Ghiso J (2005) Chromosome 13 dementias. Cell Mol Life Sci 62:1814–1825. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 68. Saido T, Iwatsubo T, Mann DM, Shimada H, Ihara Y, Kawashima S (1995) Dominant and differential deposition of distinct b‐amyloid peptide species, AbN3(pE), in senile plaques. Neuron 14:457–466. [DOI] [PubMed] [Google Scholar]
  • 69. Saido T, Yamao‐Harigaya W, Iwatsubo T, Kawashima S (1996) Amino‐and carboxyl‐terminal heterogeneity of beta‐amyloid peptides deposited in human brain. Neurosci Letts 13:173–176. [DOI] [PubMed] [Google Scholar]
  • 70. Sanchez‐Pulido L, Devos D, Valencia A (2002) BRICHOS: a conserved domain in proteins associated with dementia, respiratory distress and cancer. Trends Biochem Sci 27:329–332. [DOI] [PubMed] [Google Scholar]
  • 71. Small DH (1998) The amyloid cascade hypothesis debate: emerging consensus on the role of A beta and amyloid in Alzheimer's disease. Amyloid: Intl J Exp Clin Invest 5:301–304. [DOI] [PubMed] [Google Scholar]
  • 72. Strömgren E (1981) Heredopathia ophthalmo‐otoencephalica. In: Handbook of Clinical Neurology, vol 42, Vinken, PJ . Bruyn, GW , (eds.) pp. 150–152.North Holland Publishing Co.: Amsterdam . [Google Scholar]
  • 73. Strömgren E, Dalby A, Dalby MA, Ranheim B (1970) Cataract, deafness, cerebellar ataxia, psychosis and dementia: A new syndrome. Acta Neurol Scand 46:261–262. [DOI] [PubMed] [Google Scholar]
  • 74. Su JH, Anderson AJ, Cummings BJ, Cotman CW (1994) Immunohistochemical evidence for apoptosis in Alzheimer's disease. Neuro Report 5:2529–2533. [DOI] [PubMed] [Google Scholar]
  • 75. Sykes PA, Watson SJ, Temple JS, Bateman RCJ (1999) Evidence for tissue‐specific forms of glutaminylcyclase. FEBS Lett 455:159–161. [DOI] [PubMed] [Google Scholar]
  • 76. Takuma K, Yan SD, Stern D, Yamada K (2005) Mitochondrial dysfunction, Endoplasmic reticulum stress, and apoptosis in Alzheimer's disease. J Pharmacol Sci 97:312–316. [DOI] [PubMed] [Google Scholar]
  • 77. Tekirian T, Saido T, Markesbery W, Russell M, Wekstein D, Patel E, Geddes J (1998) N‐terminal heterogeneity of parenchymal and cerebro‐vascular Ab deposits. J Neuropathol Exp Neurol 57:76–94. [DOI] [PubMed] [Google Scholar]
  • 78. Tenner AJ (2001) Complement in Alzheimer's disease: opportunities for modulating protective and pathogenic events. Neurobiol Aging 22:849–861. [DOI] [PubMed] [Google Scholar]
  • 80. Tomidokoro Y, Lashley T, Rostagno A, Zhao Z, Neubert TA, Bojsen‐Moller M, Braendgaard H, Plant G, Holton J, Frangione B, et al (2005) Familial Danish dementia: Co‐existence of A Dan and Aβ amyloid subunits in the absence of compact plaques. J Biol Chem 280:36883–36894. [DOI] [PubMed] [Google Scholar]
  • 81. Vidal R, Calero M, Revesz T, Plant G, Ghiso J, Frangione B (2001) Sequence, genomic structure and tissue expression of human BRI3, a member of the BRI gene family. Gene 266:95–102. [DOI] [PubMed] [Google Scholar]
  • 82. Vidal R, Frangione B, Rostagno A, Mead S, Revesz T, Plant G, Ghiso J (1999) A stop‐codon mutation in the BRI gene associated with familial British dementia. Nature 399:776–781. [DOI] [PubMed] [Google Scholar]
  • 83. Vidal R, Ghiso J, Revesz T, Rostagno A, Kim E, Holton J, Bek T, Bojsen‐Moller M, Braendgaard H, Plant G, et al (2000) A decamer duplication in the 3' region of the BRI gene originates a new amyloid peptide that is associated with dementia in a Danish kindred. Proc Natl Acad Sci U S A 97:4920–4925. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 84. Volles MJ, Lansbury PT (2003) Zeroing in on the pathogenic form of β‐synuclein and its mechanism of neurotoxicity in Parkinson's disease. Biochemistry 42:7871–7878. [DOI] [PubMed] [Google Scholar]
  • 85. Walsh DM, Klyubin I, Fadeeva JV, Cullen WK, Anwyl R, Wolfe MS, Rowan MJ, Selkoe DJ (2002) Naturally secreted oligomers of amyloid beta protein potently inhibit hippocampal long‐term potentiation in vivo. Nature 416:535–539. [DOI] [PubMed] [Google Scholar]
  • 86. Worster‐Drought C, Greenfield JG, McMenemey W (1940) A form of familial presenile dementia with spastic paralysis (including the pathological examination of a case). Brain 63:237–254. [Google Scholar]
  • 87. Worster‐Drought C, Hill T, McMenemey W (1933) Familial presenile dementia with spastic paralysis. J Neurol Psychopathol 14:27–34. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 88. Yakovlev AG, Faden AI (2004) Mechanisms of neural cell death: implications for development of neuroprotective treatment strategies. NeuroRx 1:5–16. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 89. Yankner BA, Duffy LK, Kirschner D (1990) Neurotrophic and neurotoxic effects of amyloid β protein: reversal by tachykinin neuropeptides. Science 250:279–282. [DOI] [PubMed] [Google Scholar]

Articles from Brain Pathology are provided here courtesy of Wiley

RESOURCES