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Does Aβ 42 Have a Function Related to Blood Homeostasis?

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Abstract

In this review, I discuss the possibility that Aβ42 has a physiologic function in blood vessel homeostasis and the consequences that this might have for theories concerning the pathogenesis of Alzheimer’s disease and for treatment.

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References

  1. Hardy JA, Higgins GA (1992) Alzheimer’s disease: the amyloid cascade hypothesis. Science 256(5054):184–185

    Article  PubMed  CAS  Google Scholar 

  2. Hardy J, Selkoe DJ (2002) The amyloid hypothesis of Alzheimer’s disease: progress and problems on the road to therapeutics. Science 297(5580):353–356

    Article  PubMed  CAS  Google Scholar 

  3. Miyakawa T, Shimoji A, Kuramoto R, Higuchi Y (1982) The relationship between senile plaques and cerebral blood vessels in Alzheimer’s disease and senile dementia. Morphological mechanism of senile plaque production. Virchows Arch B Cell Pathol Incl Mol Pathol 40:121–129

    Article  PubMed  CAS  Google Scholar 

  4. Hardy JA, Mann DMA, Wester P, Winblad B (1986) An integrative hypothesis concerning the pathogenesis and progression of Alzheimer’s disease. Neurobiol Aging 7:489–502

    Article  PubMed  CAS  Google Scholar 

  5. Levy E, Frangione B (1991) Familial Alzheimer’s disease. Curr Biol 1(5):312–314

    Article  PubMed  CAS  Google Scholar 

  6. Hendriks L, van Duijn CM, Cras P, Cruts M, Van Hul W, van Harskamp F, Warren A, McInnis MG, Antonarakis SE, Martin JJ et al. (1992) Presenile dementia and cerebral haemorrhage linked to a mutation at codon 692 of the beta-amyloid precursor protein gene. Nat Genet 1(3):218–221

    Article  PubMed  CAS  Google Scholar 

  7. Rovelet-Lecrux A, Hannequin D, Raux G, Le Meur N, Laquerriere A, Vital A, Dumanchin C, Feuillette S, Brice A, Vercelletto M, Dubas F, Frebourg T, Campion D (2006) APP locus duplication causes autosomal dominant early-onset Alzheimer disease with cerebral amyloid angiopathy. Nat Genet 38(1):24–26

    Article  PubMed  CAS  Google Scholar 

  8. Kumar-Singh S, Pirici D, McGowan E, Serneels S, Ceuterick C, Hardy J, Duff K, Dickson D, Van Broeckhoven C (2005) Dense-core plaques in Tg2576 and PSAPP mouse models of Alzheimer’s disease are centered on vessel walls. Am J Pathol 167(2):527–543

    PubMed  CAS  Google Scholar 

  9. Falangola MF, Lee SP, Nixon RA, Duff K, Helpern JA (2005) Histological co-localization of iron in Abeta plaques of PS/APP transgenic mice. Neurochem Res 30(2):201–205

    Article  PubMed  CAS  Google Scholar 

  10. Cullen KE, Kocsi Z, Stone J. Microvascular pathology in the aging human brain: Evidence that senile plaques are sites of microhaemorrhages. Neurobiol Aging (in press)

  11. Van Nostrand WE, Schmaier AH, Farrow JS, Cunningham DD (1990) Protease nexin-II (amyloid beta-protein precursor): a platelet alpha-granule protein. Science 248(4956):745–748

    Article  PubMed  Google Scholar 

  12. Goldgaber D, Harris HW, Hla T, Maciag T, Donnelly RJ, Jacobsen JS, Vitek MP, Gajdusek DC (1989) Interleukin 1 regulates synthesis of amyloid beta-protein precursor mRNA in human endothelial cells. Proc Natl Acad Sci USA 86(19):7606–7610

    Article  PubMed  CAS  Google Scholar 

  13. Kotilinek LA, Bacskai B, Westerman M, Kawarabayashi T, Younkin L, Hyman BT, Younkin S, Ashe KH (2002) Reversible memory loss in a mouse transgenic model of Alzheimer’s disease. J Neurosci 22(15):6331–6335

    PubMed  CAS  Google Scholar 

  14. Tanzi RE (2005) The synaptic Abeta hypothesis of Alzheimer disease. Nat Neurosci 8(8):977–979

    Article  PubMed  CAS  Google Scholar 

  15. 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, Viitanen M, Peskind E, Poorkaj P, Schellenberg G, Tanzi R, Wasco W, Lannfelt L, Selkoe D, Younkin S (1996) Secreted amyloid beta-protein 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(8):864–870

    Article  PubMed  CAS  Google Scholar 

  16. Beglopoulos V, Shen J (2006) Regulation of CRE-dependent transcription by presenilins: prospects for therapy of Alzheimer’s disease. Trends Pharmacol Sci 27(1):33–40

    Article  PubMed  CAS  Google Scholar 

  17. Rapoport M, Dawson H, Binder LI., Vitek MP, Ferreira A (2002) Tau is essential to β-amyloid-induced neurotoxicity. Proc Natl Acad Sci (USA) 99:6364–6369

    Article  CAS  Google Scholar 

  18. Lewis J, Dickson DW, Lin WL, Chisholm L, Corral A, Jones G, Yen SH, Sahara N, Skipper L, Yager D, Eckman C, Hardy J, Hutton M, McGowan E (2001) Enhanced neurofibrillary degeneration in transgenic mice expressing mutant tau and APP. Science 293(5534):1487–1491

    Article  PubMed  CAS  Google Scholar 

  19. Atwood CS, Bowen RL, Smith MA, Perry G (2003) Cerebrovascular requirement for sealant, anti-coagulant and remodeling molecules that allow for the maintenance of vascular integrity and blood supply. Brain Res Brain Res Rev 43(1):164–178

    Article  PubMed  CAS  Google Scholar 

  20. Weller RO, Massey A, Newman TA, Hutchings M, Kuo YM, Roher AE (1998) Cerebral amyloid angiopathy: amyloid beta accumulates in putative interstitial fluid drainage pathways in Alzheimer’s disease. Am J Pathol 153:725–733

    PubMed  CAS  Google Scholar 

  21. McCarron MO, Nicoll JA (2000) Apolipoprotein E genotype and cerebral amyloid angiopathy-related hemorrhage. Ann N Y Acad Sci 903:176–179

    Article  PubMed  CAS  Google Scholar 

  22. Thomas T, Thomas G, McLendon C, Sutton T, Mullan M (1996) beta-Amyloid-mediated vasoactivity and vascular endothelial damage. Nature 380(6570):168–171

    Article  PubMed  CAS  Google Scholar 

  23. Miao J, Vitek MP, Xu F, Previti ML, Davis J, Van Nostrand WE (2005) Reducing cerebral microvascular amyloid-beta protein deposition diminishes regional neuroinflammation in vasculotropic mutant amyloid precursor protein transgenic mice. J Neurosci 25(27):6271–6277

    Article  PubMed  CAS  Google Scholar 

  24. Atwood CS, Perry G, Smith MA (2003) Cerebral hemorrhage and amyloid-beta. Science 299(5609):1014

    Article  PubMed  CAS  Google Scholar 

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Acknowledgment

Work in the author’s lab was supported by the NIA/NIH intramural program.

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Authors and Affiliations

  1. Laboratory of Neurogenetics, NIA, Porter Neuroscience Building, NIH Main Campus, Bethesda, MD, 20892, USA

    John Hardy

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  1. John Hardy
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Correspondence to John Hardy.

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Dedicated with affection to John Blass, who is always willing to talk about new ideas.

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Hardy, J. Does Aβ 42 Have a Function Related to Blood Homeostasis?. Neurochem Res 32, 833–835 (2007). https://doi.org/10.1007/s11064-006-9221-9

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  • DOI: https://doi.org/10.1007/s11064-006-9221-9

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