Study of neurodegenerative diseases with novel MRI techniques
Author: Li, Xiaozhen
Date: 2015-06-09
Location: Lecture Hall 4th floor, Novum, Karolinska Institute, Huddinge
Time: 09.30AM
Department: Inst för neurobiologi, vårdvetenskap och samhälle / Dept of Neurobiology, Care Sciences and Society
View/ Open:
Thesis (8.959Mb)
Abstract
Neurodegenerative diseases are a heterogeneous group of disorders that are
characterized by the progressive degeneration of structure and function of the nervous
system. They include diseases such as Alzheimer’s disease (AD), multiple sclerosis
(MS) and others. The main aims of this thesis were to study functional and/or
structural brain changes in AD and MS using novel magnetic resonance imaging
(MRI) techniques.
The concentration of β-amyloid1-42 (Aβ42), total tau (T-tau) and tau phosphorylated at position threonine 181 (P-tau181p) in cerebrospinal fluid (CSF) may reflect brain pathophysiological processes in AD. We found a positive correlation between functional connectivity within the default mode network (DMN) and the ratio of Aβ42/P-tau181p in sporadic AD (Paper I). Furthermore, there were correlations between AD CSF biomarkers and changes of gray matter volume, fractional anisotropy (FA) and mean diffusivity (MD). The majority of brain regions with statistically significant correlation with biomarkers of AD overlapped with the DMN (Paper II). These findings implicate that the brain functional connectivity and structure are affected by pathological changes at an early stage in AD. We also found a significantly increased MD in pre-symptomatic mutation carriers (pre-MCs) of AD compared with non-carriers (NCs), and increased MD associated with AD CSF biomarkers (Paper III). Similar results were observed both in sporadic and familial AD, which suggests that MD may reflect pathology of early stage AD. Although the exact causes of these changes are difficult to identify, the increased MD may be explained by myelin loss. In MS, myelin loss is one of the characteristic events of the pathological process. By combining susceptibility-weighted MRI with analysis of the 𝑇! ∗ decay curves, we were able to characterize and quantify myelin loss (Paper IV).
In conclusion, pathological changes in AD and MS could be detected by novel MRI techniques. This suggests that these techniques may also be helpful in further understanding pathology in other neurodegenerative diseases. As non-invasive tools, these novel MRI techniques are possible to screen individuals susceptible to and/or manifesting early neurodegeneration.
The concentration of β-amyloid1-42 (Aβ42), total tau (T-tau) and tau phosphorylated at position threonine 181 (P-tau181p) in cerebrospinal fluid (CSF) may reflect brain pathophysiological processes in AD. We found a positive correlation between functional connectivity within the default mode network (DMN) and the ratio of Aβ42/P-tau181p in sporadic AD (Paper I). Furthermore, there were correlations between AD CSF biomarkers and changes of gray matter volume, fractional anisotropy (FA) and mean diffusivity (MD). The majority of brain regions with statistically significant correlation with biomarkers of AD overlapped with the DMN (Paper II). These findings implicate that the brain functional connectivity and structure are affected by pathological changes at an early stage in AD. We also found a significantly increased MD in pre-symptomatic mutation carriers (pre-MCs) of AD compared with non-carriers (NCs), and increased MD associated with AD CSF biomarkers (Paper III). Similar results were observed both in sporadic and familial AD, which suggests that MD may reflect pathology of early stage AD. Although the exact causes of these changes are difficult to identify, the increased MD may be explained by myelin loss. In MS, myelin loss is one of the characteristic events of the pathological process. By combining susceptibility-weighted MRI with analysis of the 𝑇! ∗ decay curves, we were able to characterize and quantify myelin loss (Paper IV).
In conclusion, pathological changes in AD and MS could be detected by novel MRI techniques. This suggests that these techniques may also be helpful in further understanding pathology in other neurodegenerative diseases. As non-invasive tools, these novel MRI techniques are possible to screen individuals susceptible to and/or manifesting early neurodegeneration.
List of papers:
I. XIAOZHEN LI, Tie-Qiang Li, Niels Andreasen, Maria Kristoffersen Wiberg, Eric Westman, Lars-Olof Wahlund. Ratio of Aβ42/P-tau181p in CSF is associated with aberrant default mode network in AD. Sci Rep. 2013; 3: 1339
Fulltext (DOI)
Pubmed
View record in Web of Science®
II. XIAOZHEN LI, Tie-Qiang Li, Niels Andreasen, Maria Kristoffersen Wiberg, Eric Westman, Lars-Olof Wahlund. The association between biomarkers in cerebrospinal fluid and structural changes in the brain in patients with Alzheimer’s disease. J Intern Med. 2014; 275(4): 418-27.
Fulltext (DOI)
Pubmed
View record in Web of Science®
III. XIAOZHEN LI, Eric Westman, Anne Kinhult Ståhlbom, Steinunn Thordardottir, Ove Almkvist, Kaj Blennow, Lars-Olof Wahlund, Caroline Graff White matter changes in familial Alzheimer’s Disease. J Intern Med. 2015 Jan 31. [Epub ahead of print]
Fulltext (DOI)
Pubmed
IV. XIAOZHEN LI, Peter van Gelderen, Pascal Sati, Jacco A. de Zwart, Daniel S. Reich, Jeff H. Duyn Detection of demyelination in multiple sclerosis by analysis of T2* relaxation at 7T. Neuroimage Clin. 2015; 7:709-714
Fulltext (DOI)
I. XIAOZHEN LI, Tie-Qiang Li, Niels Andreasen, Maria Kristoffersen Wiberg, Eric Westman, Lars-Olof Wahlund. Ratio of Aβ42/P-tau181p in CSF is associated with aberrant default mode network in AD. Sci Rep. 2013; 3: 1339
Fulltext (DOI)
Pubmed
View record in Web of Science®
II. XIAOZHEN LI, Tie-Qiang Li, Niels Andreasen, Maria Kristoffersen Wiberg, Eric Westman, Lars-Olof Wahlund. The association between biomarkers in cerebrospinal fluid and structural changes in the brain in patients with Alzheimer’s disease. J Intern Med. 2014; 275(4): 418-27.
Fulltext (DOI)
Pubmed
View record in Web of Science®
III. XIAOZHEN LI, Eric Westman, Anne Kinhult Ståhlbom, Steinunn Thordardottir, Ove Almkvist, Kaj Blennow, Lars-Olof Wahlund, Caroline Graff White matter changes in familial Alzheimer’s Disease. J Intern Med. 2015 Jan 31. [Epub ahead of print]
Fulltext (DOI)
Pubmed
IV. XIAOZHEN LI, Peter van Gelderen, Pascal Sati, Jacco A. de Zwart, Daniel S. Reich, Jeff H. Duyn Detection of demyelination in multiple sclerosis by analysis of T2* relaxation at 7T. Neuroimage Clin. 2015; 7:709-714
Fulltext (DOI)
Institution: Karolinska Institutet
Supervisor: Wahlund, Lars-Olof
Issue date: 2015-05-19
Rights:
Publication year: 2015
ISBN: 978-91-7549-970-3
Statistics
Total Visits
Views | |
---|---|
Study ...(legacy) | 279 |
Study ... | 153 |
Total Visits Per Month
September 2023 | October 2023 | November 2023 | December 2023 | January 2024 | February 2024 | March 2024 | |
---|---|---|---|---|---|---|---|
Study ... | 1 | 2 | 0 | 0 | 0 | 0 | 1 |
File Visits
Views | |
---|---|
Thesis_Xiaozhen_Li.pdf(legacy) | 351 |
Thesis_Xiaozhen_Li.pdf | 296 |
Top country views
Views | |
---|---|
United States | 96 |
Sweden | 69 |
Germany | 40 |
China | 38 |
Finland | 8 |
Ireland | 7 |
South Korea | 6 |
United Kingdom | 5 |
Russia | 5 |
Greece | 4 |
Top cities views
Views | |
---|---|
Ashburn | 46 |
Beijing | 19 |
Stockholm | 19 |
Kiez | 15 |
Dublin | 6 |
Seoul | 6 |
Sunnyvale | 5 |
Woodbridge | 5 |
Athens | 4 |
Des Moines | 3 |