Home LiteratureArticle Details
PMID: 19524115 Published · ppublish English Comparative Study Journal Article Research Support, Non-U.S. Gov't

Comparison of Abeta levels in the brain of familial and sporadic Alzheimer's disease.

Neurochemistry international ·Vol. 55 ·No. 4 ·2009-09-00 ·Pages 243-52

Hellström-Lindahl E, Viitanen M, Marutle A

Abstract

Mutations in presenilin (PS) and amyloid precursor protein (APP) genes are a predominant cause for early-onset familial Alzheimer disease (AD). Although these mutations are rare, they have in the past decades advanced our understanding of the underlying molecular mechanisms of AD. In the present study, Abeta levels were measured in cortical regions of APPsw and PS1 (M146V) mutation carriers, sporadic AD (SAD) and age-matched non-demented individuals. We found similar levels of soluble Abeta42, insoluble and soluble Abeta40 in both APPsw mutation carriers and SAD. However, lower levels of insoluble Abeta42 were detected in the frontal and temporal cortex of APPsw brain. In PS1 brain, insoluble Abeta40 and Abeta42 levels were significantly lower in all four cortical regions compared with SAD, whilst levels of Abeta40 were lower in frontal and occipital cortex compared with APPsw brain. The insoluble Abeta42/40 ratio was similar in SAD and APPsw but significantly higher in PS1 mutation carriers. Our results indicate that the pattern of Abeta deposition in PS1 mutation carriers differs from that in both APPsw and SAD, whereas the pattern in APPsw mutation carriers is more similar to that in SAD.

MeSH Terms
Adult Aged Aged, 80 and over Alzheimer Disease/metabolism,pathology,physiopathology Amyloid beta-Peptides/analysis,metabolism Brain/metabolism,pathology Cerebral Cortex/metabolism,pathology DNA Mutational Analysis Family Health Female Genetic Predisposition to Disease/genetics Genetic Testing Humans Male Middle Aged Mutation/genetics Peptide Fragments/analysis,metabolism Plaque, Amyloid/metabolism,pathology Presenilin-1/genetics
Chemicals
Amyloid beta-Peptides Peptide Fragments Presenilin-1 amyloid beta-protein (1-40) amyloid beta-protein (1-42)
Authors & Affiliations
3 authors, click to expand affiliations / ORCID
Hellström-Lindahl E
Karolinska Institutet, Department of Neurobiology, Care Sciences and Society, Division of Alzheimer Neurobiology, Sweden. [email protected]
Viitanen M
Marutle A
References (55)
55 references, click to expand
  1. Abeta42 is essential for parenchymal and vascular amyloid deposition in mice.
    Neuron. 2005 Jul 21;47(2):191-199 PMID: 16039562
  2. The presenilin hypothesis of Alzheimer's disease: evidence for a loss-of-function pathogenic mechanism.
    Proc Natl Acad Sci U S A. 2007 Jan 9;104(2):403-9 PMID: 17197420
  3. Mean age of onset in familial Alzheimer's disease is determined by amyloid beta 42.
    Neurobiol Aging. 2005 Jun;26(6):785-8 PMID: 15718035
  4. Decreased Abeta secretion by cells expressing familial Alzheimer's disease-linked mutant presenilin 1.
    Neurosci Res. 2007 Mar;57(3):446-53 PMID: 17210196
  5. 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. 1996 Aug;2(8):864-70 PMID: 8705854
  6. The carboxy terminus of the beta amyloid protein is critical for the seeding of amyloid formation: implications for the pathogenesis of Alzheimer's disease.
    Biochemistry. 1993 May 11;32(18):4693-7 PMID: 8490014
  7. Clinical diagnosis of Alzheimer's disease: report of the NINCDS-ADRDA Work Group under the auspices of Department of Health and Human Services Task Force on Alzheimer's Disease.
    Neurology. 1984 Jul;34(7):939-44 PMID: 6610841
  8. Amyloid beta protein (Abeta) deposition in chromosome 14-linked Alzheimer's disease: predominance of Abeta42(43).
    Ann Neurol. 1996 Aug;40(2):149-56 PMID: 8773595
  9. Neurofibrillary tangles but not senile plaques parallel duration and severity of Alzheimer's disease.
    Neurology. 1992 Mar;42(3 Pt 1):631-9 PMID: 1549228
  10. Age-dependent changes in brain, CSF, and plasma amyloid (beta) protein in the Tg2576 transgenic mouse model of Alzheimer's disease.
    J Neurosci. 2001 Jan 15;21(2):372-81 PMID: 11160418
  11. Neuronal nicotinic receptor deficits in Alzheimer patients with the Swedish amyloid precursor protein 670/671 mutation.
    J Neurochem. 1999 Mar;72(3):1161-9 PMID: 10037489
  12. Enhanced generation of intracellular Abeta42 amyloid peptide by mutation of presenilins PS1 and PS2.
    Eur J Neurosci. 2004 Jan;19(2):258-264 PMID: 14725619
  13. Physical basis of cognitive alterations in Alzheimer's disease: synapse loss is the major correlate of cognitive impairment.
    Ann Neurol. 1991 Oct;30(4):572-80 PMID: 1789684
  14. Alzheimer's disease: molecular understanding predicts amyloid-based therapeutics.
    Annu Rev Pharmacol Toxicol. 2003;43:545-84 PMID: 12415125
  15. High-level neuronal expression of abeta 1-42 in wild-type human amyloid protein precursor transgenic mice: synaptotoxicity without plaque formation.
    J Neurosci. 2000 Jun 1;20(11):4050-8 PMID: 10818140
  16. Tangles and plaques in nondemented aging and "preclinical" Alzheimer's disease.
    Ann Neurol. 1999 Mar;45(3):358-68 PMID: 10072051
  17. Amyloid beta protein (A beta) in Alzheimer's disease brain. Biochemical and immunocytochemical analysis with antibodies specific for forms ending at A beta 40 or A beta 42(43).
    J Biol Chem. 1995 Mar 31;270(13):7013-6 PMID: 7706234
  18. Familial Alzheimer's disease-linked presenilin 1 variants elevate Abeta1-42/1-40 ratio in vitro and in vivo.
    Neuron. 1996 Nov;17(5):1005-13 PMID: 8938131
  19. Effect of apolipoprotein E allele epsilon4 on the initial phase of amyloid beta-protein accumulation in the human brain.
    Am J Pathol. 2000 Dec;157(6):2093-9 PMID: 11106581
  20. The impact of different presenilin 1 andpresenilin 2 mutations on amyloid deposition, neurofibrillary changes and neuronal loss in the familial Alzheimer's disease brain: evidence for other phenotype-modifying factors.
    Brain. 1999 Sep;122 ( Pt 9):1709-19 PMID: 10468510
  21. A large Swedish family with Alzheimer's disease with a codon 670/671 amyloid precursor protein mutation. A clinical and genealogical investigation.
    Arch Neurol. 1994 Dec;51(12):1193-7 PMID: 7986173
  22. Quantitation of amyloid beta-protein (A beta) in the cortex during aging and in Alzheimer's disease.
    Am J Pathol. 1998 Jun;152(6):1633-40 PMID: 9626067
  23. Molecular pathogenesis of sporadic and familial forms of Alzheimer's disease.
    Mol Med Today. 1998 Apr;4(4):151-7 PMID: 9572056
  24. Mean age-of-onset of familial alzheimer disease caused by presenilin mutations correlates with both increased Abeta42 and decreased Abeta40.
    Hum Mutat. 2006 Jul;27(7):686-95 PMID: 16752394
  25. Mutation of the beta-amyloid precursor protein in familial Alzheimer's disease increases beta-protein production.
    Nature. 1992 Dec 17;360(6405):672-4 PMID: 1465129
  26. Enhanced production and oligomerization of the 42-residue amyloid beta-protein by Chinese hamster ovary cells stably expressing mutant presenilins.
    J Biol Chem. 1997 Mar 21;272(12):7977-82 PMID: 9065468
  27. Deletion of presenilin 1 hydrophilic loop sequence leads to impaired gamma-secretase activity and exacerbated amyloid pathology.
    J Neurosci. 2006 Apr 5;26(14):3845-54 PMID: 16597739
  28. Increased amyloid-beta42(43) in brains of mice expressing mutant presenilin 1.
    Nature. 1996 Oct 24;383(6602):710-3 PMID: 8878479
  29. A beta oligomers - a decade of discovery.
    J Neurochem. 2007 Jun;101(5):1172-84 PMID: 17286590
  30. APOE polymorphism and clinical duration determine regional neuropathology in Swedish APP(670, 671) mutation carriers: implications for late-onset Alzheimer's disease.
    J Cell Mol Med. 2002 Apr-Jun;6(2):199-214 PMID: 12169205
  31. The pathogenesis of senile plaques.
    J Neuropathol Exp Neurol. 1997 Apr;56(4):321-39 PMID: 9100663
  32. Full-length amyloid-beta (1-42(43)) and amino-terminally modified and truncated amyloid-beta 42(43) deposit in diffuse plaques.
    Am J Pathol. 1996 Dec;149(6):1823-30 PMID: 8952519
  33. Enhancement of amyloid beta 42 secretion by 28 different presenilin 1 mutations of familial Alzheimer's disease.
    Neurosci Lett. 1999 Apr 9;265(1):61-3 PMID: 10327206
  34. The levels of soluble versus insoluble brain Abeta distinguish Alzheimer's disease from normal and pathologic aging.
    Exp Neurol. 1999 Aug;158(2):328-37 PMID: 10415140
  35. Soluble protein oligomers in neurodegeneration: lessons from the Alzheimer's amyloid beta-peptide.
    Nat Rev Mol Cell Biol. 2007 Feb;8(2):101-12 PMID: 17245412
  36. Mutant presenilins of Alzheimer's disease increase production of 42-residue amyloid beta-protein in both transfected cells and transgenic mice.
    Nat Med. 1997 Jan;3(1):67-72 PMID: 8986743
  37. Familial and sporadic Alzheimer's disease: neuropathology cannot exclude a final common pathway.
    Neurology. 1996 Feb;46(2):406-12 PMID: 8614503
  38. Amyloid angiopathy and variability in amyloid beta deposition is determined by mutation position in presenilin-1-linked Alzheimer's disease.
    Am J Pathol. 2001 Jun;158(6):2165-75 PMID: 11395394
  39. Soluble amyloid beta peptide concentration as a predictor of synaptic change in Alzheimer's disease.
    Am J Pathol. 1999 Sep;155(3):853-62 PMID: 10487842
  40. Abeta40 inhibits amyloid deposition in vivo.
    J Neurosci. 2007 Jan 17;27(3):627-33 PMID: 17234594
  41. Pathological and clinical heterogeneity of presenilin 1 gene mutations.
    J Alzheimers Dis. 2004 Oct;6(5):475-82 PMID: 15505368
  42. Alzheimer's disease: genes, proteins, and therapy.
    Physiol Rev. 2001 Apr;81(2):741-66 PMID: 11274343
  43. Clinical, pathological, and biochemical spectrum of Alzheimer disease associated with PS-1 mutations.
    Am J Geriatr Psychiatry. 2004 Mar-Apr;12(2):146-56 PMID: 15010344
  44. Distinct early folding and aggregation properties of Alzheimer amyloid-beta peptides Abeta40 and Abeta42: stable trimer or tetramer formation by Abeta42.
    J Biol Chem. 2006 Aug 25;281(34):24414-22 PMID: 16809342
  45. Predominant deposition of amyloid-beta 42(43) in plaques in cases of Alzheimer's disease and hereditary cerebral hemorrhage associated with mutations in the amyloid precursor protein gene.
    Am J Pathol. 1996 Apr;148(4):1257-66 PMID: 8644866
  46. Chromosome 14-encoded Alzheimer's disease: genetic and clinicopathological description.
    Ann Neurol. 1994 Sep;36(3):362-7 PMID: 8080244
  47. Reduced levels of Abeta 40 and Abeta 42 in brains of smoking controls and Alzheimer's patients.
    Neurobiol Dis. 2004 Mar;15(2):351-60 PMID: 15006705
  48. Biogenesis and metabolism of Alzheimer's disease Abeta amyloid peptides.
    Peptides. 2002 Jul;23(7):1285-97 PMID: 12128085
  49. Presenilin clinical mutations can affect gamma-secretase activity by different mechanisms.
    J Neurochem. 2006 Feb;96(3):732-42 PMID: 16405513
  50. Amyloid-beta-protein isoforms in brain of subjects with PS1-linked, beta APP-linked and sporadic Alzheimer disease.
    Brain Res Mol Brain Res. 1998 May;56(1-2):178-85 PMID: 9602117
  51. Age-dependent decline of neprilysin in Alzheimer's disease and normal brain: inverse correlation with A beta levels.
    Neurobiol Aging. 2008 Feb;29(2):210-21 PMID: 17098332
  52. Mutant presenilins specifically elevate the levels of the 42 residue beta-amyloid peptide in vivo: evidence for augmentation of a 42-specific gamma secretase.
    Hum Mol Genet. 2004 Jan 15;13(2):159-70 PMID: 14645205
  53. Phases of A beta-deposition in the human brain and its relevance for the development of AD.
    Neurology. 2002 Jun 25;58(12):1791-800 PMID: 12084879
  54. Amyloid precursor protein mutation causes Alzheimer's disease in a Swedish family.
    Neurosci Lett. 1994 Feb 28;168(1-2):254-6 PMID: 8028788
  55. Loss-of-function presenilin mutations in Alzheimer disease. Talking Point on the role of presenilin mutations in Alzheimer disease.
    EMBO Rep. 2007 Feb;8(2):141-6 PMID: 17268505
Article Info
Journal
Neurochemistry international
Abbr.
Neurochem Int
ISSN
1872-9754
DOI
10.1016/j.neuint.2009.03.007
Email
[email protected]
Published
2009-09-00
Epub
2009-00-20
Pages
243-52
Language
English
Region
England
NLM ID
8006959
PMCID
PMC2919843
Subset
IM
Grants
NIA NIH HHS · R01 AG021975-03 · United States
NIA NIH HHS · R01 AG021975-04 · United States
NIA NIH HHS · R01 AG021975-02 · United States
NIA NIH HHS · R01 AG021975-01A2 · United States
NIA NIH HHS · R01 AG021975 · United States
External Links
PubMed source DOI: 10.1016/j.neuint.2009.03.007 PMC Full Text View journal details
Analysis Services
Analysis Services

Contact

No. 2 Wenbo Road, Zhangqiu District, Jinan, Shandong

Qilu Normal University · Genelibs Bioinformatics Lab

750 Shunhua Rd, Jinan

2F, Bldg F, University Science Park

Tel: 0531-88819269

WeChat Official Account

Follow our WeChat subscription account for real-time updates and the latest in medical and biological research.


Business Email

E-mail: [email protected]

Copyright © 2026.Genelibs Jinan Honghui Biotechnology Co., Ltd. 鲁ICP备20007159号-2