Skip to main content
Key Specialties
Cardiology Diabetology Endocrinology Gastroenterology Geriatrics and Gerontology Gynecology and Obstetrics Hematology Infectious Disease Internal Medicine Nephrology Neurology Oncology Pediatrics Respiratory Medicine Rheumatology Surgery
Congress Coverage
2024 ACC Congress 2023 ESMO Congress 2023 EASD Congress 2023 ERS Congress 2023 ESC Congress
Clinical Collections
Advances in Alzheimer’s

Keynote webinar | Spotlight on medication adherence

LIVE: Thursday 27th June 2024, 18:00-19:30 (CEST)
Join our expert panel to discover why you need to understand the drivers of non-adherence in your patients, and how you can optimize medication adherence in your clinics to drastically improve patient outcomes.
ADVANCED SEARCH
Log in
Top
Acta Neuropathologica Communications
Published in: Acta Neuropathologica Communications 1/2013

Open Access 01-12-2013 | Research

Brains from non-Alzheimer’s individuals containing amyloid deposits accelerate Aβ deposition in vivo

Authors: Claudia Duran-Aniotz, Rodrigo Morales, Ines Moreno-Gonzalez, Ping Ping Hu, Claudio Soto

Published in: Acta Neuropathologica Communications | Issue 1/2013

Login to get access

Abstract

Background

One of the main features of Alzheimer’s disease (AD) is the presence of Aβ deposits, which accumulate in the brain years before the onset of symptoms. We and others have demonstrated that cerebral Aβ-amyloidosis can be induced in vivo by administration of AD-brain extracts into transgenic mice. However, it is currently unknown whether amyloid formation can be induced using extracts from individuals harboring Aβ deposits, but not clinical disease.

Results

In this study we analyzed the amyloid-inducing capability of samples from individuals affected by mild cognitive impairment (MCI) and Non-Demented persons with Alzheimer’s disease Neuropathology (NDAN). Our results show that inoculation of transgenic mice with MCI and NDAN brain samples accelerated Aβ pathology in a similar way as extracts from confirmed AD.

Conclusions

This data demonstrate that the sole presence of Aβ aggregates in a given sample, regardless of the clinical condition, is capable to accelerate Aβ deposition in vivo. These findings indicate that the amyloid-inducing activity may be present in the brain of people during pre-symptomatic or a-symptomatic stages of AD.
Appendix
Available only for authorised users
Literature
1.
Hebert LE, Scherr PA, Bienias JL, Bennett DA, Evans DA: Alzheimer disease in the US population: prevalence estimates using the 2000 census. Arch Neurol 2003, 60: 1119–1122.CrossRefPubMed
2.
Thies W, Bleiler L: Alzheimer's disease facts and figures. Alzheimers Dement 2011,2011(7):208–244.
3.
Gomez-Isla T, Spires T, de CA, Hyman BT: Neuropathology of Alzheimer's disease. Handb Clin Neurol 2008, 89: 233–243.CrossRefPubMed
4.
Estus S, Borchelt D, Kindy MS, Vassar R: Abeta deposition is essential to AD neuropathology. J Alzheimers Dis 2002, 4: 133–138.PubMed
5.
Glabe CG: Common mechanisms of amyloid oligomer pathogenesis in degenerative disease. Neurobiol Aging 2006, 27: 570–575.CrossRefPubMed
6.
Haass C, Selkoe DJ: Soluble protein oligomers in neurodegeneration: lessons from the Alzheimer's amyloid beta-peptide. Nat Rev Mol Cell Biol 2007, 8: 101–112.CrossRefPubMed
7.
8.
Murakami K, Irie K, Morimoto A, Ohigashi H, Shindo M, Nagao M, Shimizu T, Shirasawa T: Neurotoxicity and physicochemical properties of Abeta mutant peptides from cerebral amyloid angiopathy: implication for the pathogenesis of cerebral amyloid angiopathy and Alzheimer's disease. J Biol Chem 2003, 278: 46179–46187.CrossRefPubMed
9.
Oddo S, Caccamo A, Shepherd JD, Murphy MP, Golde TE, Kayed R, Metherate R, Mattson MP, Akbari Y, LaFerla FM: Triple-transgenic model of Alzheimer's disease with plaques and tangles: intracellular Abeta and synaptic dysfunction. Neuron 2003, 39: 409–421.CrossRefPubMed
10.
Nelson PT, Braak H, Markesbery WR: Neuropathology and cognitive impairment in Alzheimer disease: a complex but coherent relationship. J Neuropathol Exp Neurol 2009, 68: 1–14.PubMedCentralCrossRefPubMed
11.
Moore BD, Chakrabarty P, Levites Y, Kukar TL, Baine AM, Moroni T, Ladd TB, Das P, Dickson DW, Golde TE: Overlapping profiles of Abeta peptides in the Alzheimer's disease and pathological aging brains. Alzheimers Res Ther 2012, 4: 18.PubMedCentralCrossRefPubMed
12.
Price JL, McKeel DW Jr, Buckles VD, Roe CM, Xiong C, Grundman M, Hansen LA, Petersen RC, Parisi JE, Dickson DW, et al.: Neuropathology of nondemented aging: presumptive evidence for preclinical Alzheimer disease. Neurobiol Aging 2009, 30: 1026–1036.PubMedCentralCrossRefPubMed
13.
Jack CR Jr, Knopman DS, Jagust WJ, Petersen RC, Weiner MW, Aisen PS, Shaw LM, Vemuri P, Wiste HJ, Weigand SD, et al.: Tracking pathophysiological processes in Alzheimer's disease: an updated hypothetical model of dynamic biomarkers. Lancet Neurol 2013, 12: 207–216.PubMedCentralCrossRefPubMed
14.
Petersen RC, Parisi JE, Dickson DW, Johnson KA, Knopman DS, Boeve BF, Jicha GA, Ivnik RJ, Smith GE, Tangalos EG, et al.: Neuropathologic features of amnestic mild cognitive impairment. Arch Neurol 2006, 63: 665–672.CrossRefPubMed
15.
Wolk DA, Price JC, Saxton JA, Snitz BE, James JA, Lopez OL, Aizenstein HJ, Cohen AD, Weissfeld LA, Mathis CA, et al.: Amyloid imaging in mild cognitive impairment subtypes. Ann Neurol 2009, 65: 557–568.PubMedCentralCrossRefPubMed
16.
Dubois B, Albert ML: Amnestic MCI or prodromal Alzheimer's disease? Lancet Neurol 2004, 3: 246–248.CrossRefPubMed
17.
Petersen RC: Mild cognitive impairment: transition between aging and Alzheimer's disease. Neurologia 2000, 15: 93–101.PubMed
18.
Bennett DA, Schneider JA, Bienias JL, Evans DA, Wilson RS: Mild cognitive impairment is related to Alzheimer disease pathology and cerebral infarctions. Neurology 2005, 64: 834–841.CrossRefPubMed
19.
20.
Petersen RC, Smith GE, Waring SC, Ivnik RJ, Tangalos EG, Kokmen E: Mild cognitive impairment: clinical characterization and outcome. Arch Neurol 1999, 56: 303–308.CrossRefPubMed
21.
Erten-Lyons D, Woltjer RL, Dodge H, Nixon R, Vorobik R, Calvert JF, Leahy M, Montine T, Kaye J: Factors associated with resistance to dementia despite high Alzheimer disease pathology. Neurology 2009, 72: 354–360.PubMedCentralCrossRefPubMed
22.
Kane MD, Lipinski WJ, Callahan MJ, Bian F, Durham RA, Schwarz RD, Roher AE, Walker LC: Evidence for seeding of beta -amyloid by intracerebral infusion of Alzheimer brain extracts in beta -amyloid precursor protein-transgenic mice. J Neurosci 2000, 20: 3606–3611.PubMed
23.
Meyer-Luehmann M, Coomaraswamy J, Bolmont T, Kaeser S, Schaefer C, Kilger E, Neuenschwander A, Abramowski D, Frey P, Jaton AL, et al.: Exogenous induction of cerebral beta-amyloidogenesis is governed by agent and host. Science 2006, 313: 1781–1784.CrossRefPubMed
24.
Morales R, Duran-Aniotz C, Castilla J, Estrada LD, Soto C: De novo induction of amyloid-beta deposition in vivo. Mol Psychiatry 2012, 17: 1347–1353.CrossRefPubMed
25.
Rosen RF, Fritz JJ, Dooyema J, Cintron AF, Hamaguchi T, Lah JJ, LeVine H III, Jucker M, Walker LC: Exogenous seeding of cerebral beta-amyloid deposition in betaAPP-transgenic rats. J Neurochem 2012, 120: 660–666.PubMedCentralCrossRefPubMed
26.
Soto C, Estrada L, Castilla J: Amyloids, prions and the inherent infectious nature of misfolded protein aggregates. Trends Biochem Sci 2006, 31: 150–155.CrossRefPubMed
27.
28.
Aguzzi A, Rajendran L: The transcellular spread of cytosolic amyloids, prions, and prionoids. Neuron 2009, 64: 783–790.CrossRefPubMed
29.
30.
31.
Eisele YS, Obermuller U, Heilbronner G, Baumann F, Kaeser SA, Wolburg H, Walker LC, Staufenbiel M, Heikenwalder M, Jucker M: Peripherally applied A{beta}-containing inoculates induce cerebral {beta}-amyloidosis. Science 2010, 330: 980–982.PubMedCentralCrossRefPubMed
32.
Hamaguchi T, Eisele YS, Varvel NH, Lamb BT, Walker LC, Jucker M: The presence of Abeta seeds, and not age per se, is critical to the initiation of Abeta deposition in the brain. Acta Neuropathol 2012, 123: 31–37.PubMedCentralCrossRefPubMed
33.
Jankowsky JL, Fadale DJ, Anderson J, Xu GM, Gonzales V, Jenkins NA, Copeland NG, Lee MK, Younkin LH, Wagner SL, et al.: 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, 13: 159–170.CrossRefPubMed
34.
Garcia-Alloza M, Robbins EM, Zhang-Nunes SX, Purcell SM, Betensky RA, Raju S, Prada C, Greenberg SM, Bacskai BJ, Frosch MP: Characterization of amyloid deposition in the APPswe/PS1dE9 mouse model of Alzheimer disease. Neurobiol Dis 2006, 24: 516–524.CrossRefPubMed
35.
Stohr J, Watts JC, Mensinger ZL, Oehler A, Grillo SK, DeArmond SJ, Prusiner SB, Giles K: Purified and synthetic Alzheimer's amyloid beta (Abeta) prions. Proc Natl Acad Sci USA 2012, 109: 11025–11030.PubMedCentralCrossRefPubMed
36.
Brown P, Preece M, Brandel JP, Sato T, McShane L, Zerr I, Fletcher A, Will RG, Pocchiari M, Cashman NR, et al.: Iatrogenic Creutzfeldt-Jakob disease at the millennium. Neurology 2000, 55: 1075–1081.CrossRefPubMed
37.
Irwin DJ, Abrams JY, Schonberger LB, Leschek EW, Mills JL, Lee VM, Trojanowski JQ: Evaluation of potential infectivity of Alzheimer and Parkinson disease proteins in recipients of Cadaver-derived human growth hormone. JAMA Neurol 2013, 70: 462–468.PubMedCentralCrossRefPubMed
Metadata
Title
Brains from non-Alzheimer’s individuals containing amyloid deposits accelerate Aβ deposition in vivo
Authors
Claudia Duran-Aniotz
Rodrigo Morales
Ines Moreno-Gonzalez
Ping Ping Hu
Claudio Soto
Publication date
01-12-2013
Publisher
BioMed Central
Published in
Acta Neuropathologica Communications / Issue 1/2013
Electronic ISSN: 2051-5960
DOI
https://doi.org/10.1186/2051-5960-1-76

Other articles of this Issue 1/2013

Acta Neuropathologica Communications 1/2013 Go to the issue

Research

Immune complex formation impairs the elimination of solutes from the brain: implications for immunotherapy in Alzheimer’s disease

Research

Endogenously regulated Dab2 worsens inflammatory injury in experimental autoimmune encephalomyelitis

Research

ALDH1 is an immunohistochemical diagnostic marker for solitary fibrous tumours and haemangiopericytomas of the meninges emerging from gene profiling study

Research

Nerve hyperplasia: a unique feature of ketamine cystitis

Research

Focal cortical dysplasias in autism spectrum disorders

Research

The KDM1A histone demethylase is a promising new target for the epigenetic therapy of medulloblastoma