The association between biomarkers in cerebrospinal fluid and structural changes in the brain in patients with Alzheimer's disease.
BACKGROUND
Biochemical changes in the cerebrospinal fluid (CSF) could reflect pathophysiological processes in Alzheimer's disease (AD). However, it is still not clear how these processes correlate with grey matter (GM) volume and microstructural changes in the brain.


OBJECTIVE
To assess the relationship between CSF biomarkers and structural brain changes in AD.


METHODS
Cross-sectional study in a memory clinic-based sample.


METHODS
A total of 78 subjects were included in the study: 22 with subjective cognitive impairment (SCI), 35 with mild cognitive impairment (MCI) and 21 with AD.


METHODS
Voxel-wise correlations between CSF biomarkers, including β-amyloid42 (Aβ42), tau phosphorylated at position threonine 181 and total tau protein, and GM volume, self-diffusion fractional anisotropy (FA) and mean diffusivity (MD) maps using voxel-based morphometry and tract-based spatial statistical analyses. FA and MD maps were obtained using diffusion tensor imaging.


RESULTS
In the whole sample (patients with SCI, MCI and AD), there was positive correlation between GM volume and Aβ42 concentration, and negative correlation with total tau protein. Higher FA was only related to higher concentration of Aβ42. MD showed significant negative correlation with Aβ42 and positive correlation with T-tau levels. The majority of brain regions with significant correlation with CSF biomarkers overlapped with the default mode network and extended to the adjacent white matter.


CONCLUSIONS
Early AD pathological changes can be detected with voxel-based morphometric analysis and diffusion tensor imaging measurements. Furthermore, there was an association between CSF AD biomarkers and structural brain changes in areas related to the default mode network.
Department of Neurobiology, Care Sciences and Society, Karolinska Institutet, Stockholm, Sweden.
X
X
Li
T-Q
TQ
Li
N
N
Andreasen
M K
MK
Wiberg
E
E
Westman
L-O
LO
Wahlund
D000368:Aged; D000544:Alzheimer Disease / Q000134:cerebrospinal fluid* / Q000473:pathology* / Q000503:physiopathology; D016229:Amyloid beta-Peptides / Q000134:cerebrospinal fluid*; D015415:Biomarkers / Q000134:cerebrospinal fluid; D001921:Brain / Q000378:metabolism / Q000473:pathology* / Q000503:physiopathology; D060825:Cognitive Dysfunction / Q000134:cerebrospinal fluid / Q000473:pathology; D003430:Cross-Sectional Studies; D056324:Diffusion Tensor Imaging; D018450:Disease Progression; D005260:Female; D006801:Humans; D007091:Image Processing, Computer-Assisted; D008279:Magnetic Resonance Imaging; D008297:Male; D008875:Middle Aged; D009483:Neuropsychological Tests; D010446:Peptide Fragments / Q000134:cerebrospinal fluid; D010766:Phosphorylation; D011237:Predictive Value of Tests; D012680:Sensitivity and Specificity; D012720:Severity of Illness Index; D013912:Threonine / Q000378:metabolism; D016875:tau Proteins / Q000134:cerebrospinal fluid*
D016229:Amyloid beta-Peptides; D015415:Biomarkers; D010446:Peptide Fragments; C075222:amyloid beta-protein (1-42); D016875:tau Proteins; D013912:Threonine
Alzheimer's disease (AD); cerebrospinal fluid biomarkers; diffusion tensor imaging (DTI); fractional anisotropy (FA); grey matter (GM); mean diffusivity (MD)