Study of neurodegenerative diseases with novel MRI techniques

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.

List of scientific 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
https://doi.org/10.1038/srep01339

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.
https://doi.org/10.1111/joim.12164

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]
https://doi.org/10.1111/joim.12352

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
https://doi.org/10.1016/j.nicl.2015.02.021