CSF biomarkers reflecting beta-amyloid and axonal pathology in Alzheimer's disease and related conditions
| dc.contributor.author | Mattsson, Niklas | |
| dc.date.accessioned | 2011-11-18T09:53:05Z | |
| dc.date.available | 2011-11-18T09:53:05Z | |
| dc.date.issued | 2011-11-18 | |
| dc.description.abstract | Cerebrospinal fluid (CSF) biomarkers may be used to identify and monitor pathological processes in the central nervous system. CSF biomarkers in Alzheimer’s disease (AD) include β-amyloid 42 (Aβ42), total-tau (T-tau) and phosphorylated-tau (P-tau), reflecting brain amyloid, axonal and tangle pathology, respectively. This dissertation aims at defining and validating CSF biomarkers for amyloid and axonal pathology in AD and related conditions. We found that CSF Aβ42, T-tau and P-tau identified early-stage AD patients in a uniquely large multi-center study, and achieved very high diagnostic performance in a well-controlled mono-center study, with careful standardization of clinical procedures, sample handling, and laboratory performance. The distribution of CSF Aβ42, T-tau and P-tau levels differed across age groups, likely reflecting agedependent prevalence of AD-like pathology in cognitively stable individuals. In the multi-center study, differences in the measured CSF biomarker levels were seen across laboratories. To monitor this, we established an external quality control program for CSF biomarkers. This program continues to grow and currently includes over 70 laboratories world-wide. BACE1 is a key enzyme for Aβ production, and therefore an attractive therapeutic target in AD. CSF biomarkers were studied to measure pharmacodynamic effects of BACE1-inhibitors. A panel of novel biomarkers was identified that may be used to track treatment effects in clinical trials. Finally, CSF biomarkers of amyloid and axonal pathology were studied in the lysosomal disease Niemann-Pick type C and in Lyme neuroborreliosis. Both these diseases had distinctly altered markers of amyloid metabolism and axonal pathology, and the biomarkers responded to treatments. In summary, this dissertation indicates that CSF biomarkers are useful in early AD diagnosis, identification of treatment effects and monitoring of amyloid and axonal pathology across neurological diseases. It introduces a quality control program to facilitate global biomarker implementation. With the advancement of biomarkers as components of novel diagnostic criteria, knowledge of CSF biomarker alterations in different diseases will support optimal patient management. | sv |
| dc.gup.defencedate | 2011-12-09 | |
| dc.gup.defenceplace | Fredagen den 9 december 2011, kl 13.00, Mölndalsaulan, V-huset, SU/Mölndals sjukhus | sv |
| dc.gup.department | Institute of Neuroscience and Physiology. Department of Psychiatry and Neurochemistry | sv |
| dc.gup.dissdb-fakultet | SA | |
| dc.gup.mail | niklas.mattsson@neuro.gu.se | sv |
| dc.gup.origin | University of Gothenburg. Sahlgrenska Academy | sv |
| dc.identifier.isbn | 978-91-628-8366-9 | |
| dc.identifier.uri | http://hdl.handle.net/2077/27811 | |
| dc.language.iso | eng | sv |
| dc.relation.haspart | Paper I Mattsson N, Zetterberg H, Hansson O, Andreasen N, Parnetti L, Jonsson M, Herukka SK, van der Flier WM, Blankenstein MA, Ewers M, Rich K, Kaiser E, Verbeek M, Tsolaki M, Mulugeta E, Rosén E, Aarsland D, Visser PJ, Schröder J, Marcusson J, de Leon M, Hampel H, Scheltens P, Pirttilä T, Wallin A, Jönhagen ME, Minthon L, Winblad B, Blennow K. CSF biomarkers and incipient Alzheimer disease in patients with mild cognitive impairment. JAMA 2009; 302(4): 385-393.::PMID::19622817 | sv |
| dc.relation.haspart | Paper II Johansson P§, Mattsson N§, Hansson O, Wallin A, Johansson JO, Andreasson U, Zetterberg H, Blennow K, Svensson J. §contributed equally Cerebrospinal fluid biomarkers for Alzheimer’s disease – diagnostic performance in a homogeneous mono-center population. Journal of Alzheimer’s Disease. 2011; 24(3): 537-46.::PMID::21297262 | sv |
| dc.relation.haspart | Paper III Mattsson N, Rosén E, Hansson O, Andreasen N, Parnetti L, Jonsson M, Herukka SK, van der Flier WM, Blankenstein MA, Ewers M, Rich K, Kaiser E, Verbeek M, Tsolaki M, Mulugeta E, Aarsland D, Visser PJ, Schröder J, Marcusson J, de Leon M, Hampel H, Scheltens P, Wallin A, Jönhagen ME, Minthon L, Winblad B, Blennow K, Zetterberg H. Age and diagnostic performance of Alzheimer's disease CSF biomarkers. Neurology. In press. | sv |
| dc.relation.haspart | Paper IV Mattsson N, Andreasson U, Persson S, Arai H, Batish SD, Bernardini S, Bocchio-Chiavetto L, Blankenstein MA, Carrillo MC, Chalbot S, Coart E, Chiasserini D, Cutler N, Dahlfors G, Duller S, Fagan AM, Forlenza O, Frisoni GB, Galasko D, Galimberti D, Hampel H, Handberg A, Heneka MT, Herskovits AZ, Herukka SK, Holtzman DM, Humpel C, Hyman BT, Iqbal K, Jucker M, Kaeser SA, Kaiser E, Kapaki E, Kidd D, Klivenyi P, Knudsen CS, Kummer MP, Lui J, Lladó A, Lewczuk P, Li QX, Martins R, Masters C, McAuliffe J, Mercken M, Moghekar A, Molinuevo JL, Montine TJ, Nowatzke W, O'Brien R, Otto M, Paraskevas GP, Parnetti L, Petersen RC, Prvulovic D, de Reus HP, Rissman RA, Scarpini E, Stefani A, Soininen H, Schröder J, Shaw LM, Skinningsrud A, Skrogstad B, Spreer A, Talib L, Teunissen C, Trojanowski JQ, Tumani H, Umek RM, Van Broeck B, Vanderstichele H, Vecsei L, Verbeek MM, Windisch M, Zhang J, Zetterberg H, Blennow K. The Alzheimer's Association external quality control program for CSF biomarkers. Alzheimer's & Dementia. 2011; 7(4): 386-395.::PMID::21784349 | sv |
| dc.relation.haspart | Paper V Mattsson N, Rajendran L, Zetterberg H, Gustavsson M, Andreasson U, Olsson M, Brinkmalm G, Lundkvist J, Jacobson LH, Perrot L, Neumann U, Borghys H, Mercken M, Dhuyvetter D, Jeppsson F, Blennow K, Portelius E. BACE1 inhibition induces a specific cerebrospinal fluid β-amyloid pattern that identifies drug effects in the central nervous system. Manuscript. | sv |
| dc.relation.haspart | Paper VI Mattsson N, Zetterberg H, Bianconi S, Yanjanin N, Fu R, Månsson JE, Porter FD, Blennow K. γ-Secretase-dependent amyloid β is increased in Niemann-Pick type C. A cross-sectional study. Neurology 2011; 76(4): 366-72.::PMID::21205675 | sv |
| dc.relation.haspart | Paper VII Mattsson N, Bremell D, Anckarsäter R, Blennow K, Anckarsäter H, Zetterberg H, Hagberg L. Neuroinflammation in Lyme neuroborreliosis affects amyloid metabolism. BMC Neurology 2010; 10: 51.::PMID::20569437 | sv |
| dc.subject | Alzheimer's disease | sv |
| dc.subject | biomarker | sv |
| dc.subject | cerebrospinal fluid | sv |
| dc.subject | beta-amyloid | sv |
| dc.subject | axonal | sv |
| dc.subject | Niemann-Pick type C | sv |
| dc.subject | neuroborreliosis | sv |
| dc.title | CSF biomarkers reflecting beta-amyloid and axonal pathology in Alzheimer's disease and related conditions | sv |
| dc.type | text | eng |
| dc.type.degree | Doctor of Philosophy (Medicine) | sv |
| dc.type.svep | Doctoral thesis | eng |
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