CSF T-Tau/Aβ42 predicts white matter microstructure in healthy adults at risk for Alzheimer's disease.
Cerebrospinal fluid (CSF) biomarkers T-Tau and Aβ(42) are linked with Alzheimer's disease (AD), yet little is known about the relationship between CSF biomarkers and structural brain alteration in healthy adults. In this study we examined the extent to which AD biomarkers measured in CSF predict brain microstructure indexed by diffusion tensor imaging (DTI) and volume indexed by T1-weighted imaging. Forty-three middle-aged adults with parental family history of AD received baseline lumbar puncture and MRI approximately 3.5 years later. Voxel-wise image analysis methods were used to test whether baseline CSF Aβ(42), total tau (T-Tau), phosphorylated tau (P-Tau) and neurofilament light protein predicted brain microstructure as indexed by DTI and gray matter volume indexed by T1-weighted imaging. T-Tau and T-Tau/Aβ(42) were widely correlated with indices of brain microstructure (mean, axial, and radial diffusivity), notably in white matter regions adjacent to gray matter structures affected in the earliest stages of AD. None of the CSF biomarkers were related to gray matter volume. Elevated P-Tau and P-Tau/Aβ(42) levels were associated with lower recognition performance on the Rey Auditory Verbal Learning Test. Overall, the results suggest that CSF biomarkers are related to brain microstructure in healthy adults with elevated risk of developing AD. Furthermore, the results clearly suggest that early pathological changes in AD can be detected with DTI and occur not only in cortex, but also in white matter.
Geriatric Research, Education and Clinical Center (GRECC), William S. Middleton Memorial Veteran's Hospital, Madison, Wisconsin, United States of America. bbb@medicine.wisc.edu
Barbara B
BB
Bendlin
Cynthia M
CM
Carlsson
Sterling C
SC
Johnson
Henrik
H
Zetterberg
Kaj
K
Blennow
Auriel A
AA
Willette
Ozioma C
OC
Okonkwo
Aparna
A
Sodhi
Michele L
ML
Ries
Alex C
AC
Birdsill
Andrew L
AL
Alexander
Howard A
HA
Rowley
Luigi
L
Puglielli
Sanjay
S
Asthana
Mark A
MA
Sager
D000328:Adult; D000544:Alzheimer Disease / Q000175:diagnosis* / Q000235:genetics / Q000473:pathology; D016229:Amyloid beta-Peptides / Q000134:cerebrospinal fluid*; D000704:Analysis of Variance; D015415:Biomarkers / Q000134:cerebrospinal fluid*; D056324:Diffusion Tensor Imaging; D005260:Female; D006801:Humans; D008279:Magnetic Resonance Imaging; D008297:Male; D008875:Middle Aged; D009186:Myelin Sheath / Q000473:pathology*; D009483:Neuropsychological Tests; D010446:Peptide Fragments / Q000134:cerebrospinal fluid*; D010766:Phosphorylation; D021641:Recognition, Psychology / Q000502:physiology; D014922:Wisconsin; D016875:tau Proteins / Q000378:metabolism
D016229:Amyloid beta-Peptides; D015415:Biomarkers; C054369:MAPT protein, human; D010446:Peptide Fragments; C075222:amyloid beta-protein (1-42); D016875:tau Proteins