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CSF T-Tau/Aβ42 predicts white matter microstructure in healthy adults at risk for Alzheimer's disease.

Bendlin BB, Carlsson CM, Johnson SC, Zetterberg H, Blennow K, Willette AA, Okonkwo OC, Sodhi A, Ries ML, Birdsill AC, Alexander AL, Rowley HA, Puglielli L, Asthana S, Sager MA - PLoS ONE (2012)

Bottom Line: 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.

View Article: PubMed Central - PubMed

Affiliation: Geriatric Research, Education and Clinical Center (GRECC), William S. Middleton Memorial Veteran's Hospital, Madison, Wisconsin, United States of America. bbb@medicine.wisc.edu

ABSTRACT
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.

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Related in: MedlinePlus

CSF T-Tau/Aβ42 and mean diffusivity.Higher T-Tau/Aβ42 at baseline was associated with increased mean diffusivity in follow-up scanning in several brain regions, encompassing both gray and white matter. As shown above, this relationship was especially prominent in temporal lobe white matter adjacent to hippocampus, but also encompassing gray and white matter in frontal and parietal lobes, portions of occipital white matter, and small clusters in cerebellum. Results are FDR corrected for multiple comparisons (p<.05) and displayed here with a cluster size threshold of 20 or more voxels. Sections are shown in sagittal view beginning from the left side of the brain to right. Variations in the color map reflect the size of the T-statistic (indexed by the color bar at bottom).
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pone-0037720-g001: CSF T-Tau/Aβ42 and mean diffusivity.Higher T-Tau/Aβ42 at baseline was associated with increased mean diffusivity in follow-up scanning in several brain regions, encompassing both gray and white matter. As shown above, this relationship was especially prominent in temporal lobe white matter adjacent to hippocampus, but also encompassing gray and white matter in frontal and parietal lobes, portions of occipital white matter, and small clusters in cerebellum. Results are FDR corrected for multiple comparisons (p<.05) and displayed here with a cluster size threshold of 20 or more voxels. Sections are shown in sagittal view beginning from the left side of the brain to right. Variations in the color map reflect the size of the T-statistic (indexed by the color bar at bottom).

Mentions: Voxel-wise regression analysis indicated that both T-Tau and T-Tau/Aβ42 showed robust and widespread positive relationships with several of the DTI measures, specifically MD, axial and radial diffusion. These relationships were extensive in white matter and were prevalent in temporal, parietal and frontal lobes. The locations of peak T-value for MD and FA clusters obtained in the voxel-wise analysis are tabulated in Table 2 (axial and radial diffusivity results are tabulated in Table S1). The brain regions where CSF T-Tau/Aβ42 predicted MD values in the voxel-wise regression analysis are shown in Figure 1; the positive relationship between T-Tau/Aβ42 and MD is shown in Figure 2 in scatter plots from a subset of the significant clusters found in the voxel-wise regression analysis. The regional overlap between T-Tau and T-Tau/Aβ42 SPM result maps (MD, axial and radial diffusivity) was extensive, and is summarized in terms of percent overlap in Table 3.


CSF T-Tau/Aβ42 predicts white matter microstructure in healthy adults at risk for Alzheimer's disease.

Bendlin BB, Carlsson CM, Johnson SC, Zetterberg H, Blennow K, Willette AA, Okonkwo OC, Sodhi A, Ries ML, Birdsill AC, Alexander AL, Rowley HA, Puglielli L, Asthana S, Sager MA - PLoS ONE (2012)

CSF T-Tau/Aβ42 and mean diffusivity.Higher T-Tau/Aβ42 at baseline was associated with increased mean diffusivity in follow-up scanning in several brain regions, encompassing both gray and white matter. As shown above, this relationship was especially prominent in temporal lobe white matter adjacent to hippocampus, but also encompassing gray and white matter in frontal and parietal lobes, portions of occipital white matter, and small clusters in cerebellum. Results are FDR corrected for multiple comparisons (p<.05) and displayed here with a cluster size threshold of 20 or more voxels. Sections are shown in sagittal view beginning from the left side of the brain to right. Variations in the color map reflect the size of the T-statistic (indexed by the color bar at bottom).
© Copyright Policy
Related In: Results  -  Collection

Show All Figures
getmorefigures.php?uid=PMC3368882&req=5

pone-0037720-g001: CSF T-Tau/Aβ42 and mean diffusivity.Higher T-Tau/Aβ42 at baseline was associated with increased mean diffusivity in follow-up scanning in several brain regions, encompassing both gray and white matter. As shown above, this relationship was especially prominent in temporal lobe white matter adjacent to hippocampus, but also encompassing gray and white matter in frontal and parietal lobes, portions of occipital white matter, and small clusters in cerebellum. Results are FDR corrected for multiple comparisons (p<.05) and displayed here with a cluster size threshold of 20 or more voxels. Sections are shown in sagittal view beginning from the left side of the brain to right. Variations in the color map reflect the size of the T-statistic (indexed by the color bar at bottom).
Mentions: Voxel-wise regression analysis indicated that both T-Tau and T-Tau/Aβ42 showed robust and widespread positive relationships with several of the DTI measures, specifically MD, axial and radial diffusion. These relationships were extensive in white matter and were prevalent in temporal, parietal and frontal lobes. The locations of peak T-value for MD and FA clusters obtained in the voxel-wise analysis are tabulated in Table 2 (axial and radial diffusivity results are tabulated in Table S1). The brain regions where CSF T-Tau/Aβ42 predicted MD values in the voxel-wise regression analysis are shown in Figure 1; the positive relationship between T-Tau/Aβ42 and MD is shown in Figure 2 in scatter plots from a subset of the significant clusters found in the voxel-wise regression analysis. The regional overlap between T-Tau and T-Tau/Aβ42 SPM result maps (MD, axial and radial diffusivity) was extensive, and is summarized in terms of percent overlap in Table 3.

Bottom Line: 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.

View Article: PubMed Central - PubMed

Affiliation: Geriatric Research, Education and Clinical Center (GRECC), William S. Middleton Memorial Veteran's Hospital, Madison, Wisconsin, United States of America. bbb@medicine.wisc.edu

ABSTRACT
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.

Show MeSH
Related in: MedlinePlus