Neurochemical Research

, Volume 32, Issue 4–5, pp 833–835

Does Aβ 42 Have a Function Related to Blood Homeostasis?

Original Paper


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.


Genetics Amyloid Alzheimer's disease 


  1. 1.
    Hardy JA, Higgins GA (1992) Alzheimer’s disease: the amyloid cascade hypothesis. Science 256(5054):184–185PubMedCrossRefGoogle Scholar
  2. 2.
    Hardy J, Selkoe DJ (2002) The amyloid hypothesis of Alzheimer’s disease: progress and problems on the road to therapeutics. Science 297(5580):353–356PubMedCrossRefGoogle Scholar
  3. 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 40:121–129PubMedCrossRefGoogle Scholar
  4. 4.
    Hardy JA, Mann DMA, Wester P, Winblad B (1986) An integrative hypothesis concerning the pathogenesis and progression of Alzheimer’s disease. Neurobiol Aging 7:489–502PubMedCrossRefGoogle Scholar
  5. 5.
    Levy E, Frangione B (1991) Familial Alzheimer’s disease. Curr Biol 1(5):312–314PubMedCrossRefGoogle Scholar
  6. 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):218–221PubMedCrossRefGoogle Scholar
  7. 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):24–26PubMedCrossRefGoogle Scholar
  8. 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):527–543PubMedGoogle Scholar
  9. 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):201–205PubMedCrossRefGoogle Scholar
  10. 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)Google Scholar
  11. 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):745–748PubMedCrossRefGoogle Scholar
  12. 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):7606–7610PubMedCrossRefGoogle Scholar
  13. 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):6331–6335PubMedGoogle Scholar
  14. 14.
    Tanzi RE (2005) The synaptic Abeta hypothesis of Alzheimer disease. Nat Neurosci 8(8):977–979PubMedCrossRefGoogle Scholar
  15. 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):864–870PubMedCrossRefGoogle Scholar
  16. 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):33–40PubMedCrossRefGoogle Scholar
  17. 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) 99:6364–6369CrossRefGoogle Scholar
  18. 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):1487–1491PubMedCrossRefGoogle Scholar
  19. 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):164–178PubMedCrossRefGoogle Scholar
  20. 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 153:725–733PubMedGoogle Scholar
  21. 21.
    McCarron MO, Nicoll JA (2000) Apolipoprotein E genotype and cerebral amyloid angiopathy-related hemorrhage. Ann N Y Acad Sci 903:176–179PubMedCrossRefGoogle Scholar
  22. 22.
    Thomas T, Thomas G, McLendon C, Sutton T, Mullan M (1996) beta-Amyloid-mediated vasoactivity and vascular endothelial damage. Nature 380(6570):168–171PubMedCrossRefGoogle Scholar
  23. 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):6271–6277PubMedCrossRefGoogle Scholar
  24. 24.
    Atwood CS, Perry G, Smith MA (2003) Cerebral hemorrhage and amyloid-beta. Science 299(5609):1014PubMedCrossRefGoogle Scholar

Copyright information

© Springer Science+Business Media, LLC 2006

Authors and Affiliations

  1. 1.Laboratory of NeurogeneticsNIABethesdaUSA

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