Plasma phosphorylated-tau181 levels reflect white matter microstructural changes across Alzheimer’s disease progression.

Abstract The most replicated blood biomarker for monitoring Alzheimer’s disease is neurofilament light (NFL). Recent evidence revealed that the plasma level of the NFL has a strong predictive value in cognitive decline and is elevated in AD patients. The Diffusion Tensor Imaging (DTI) is understood to reflect white matter disruption, neurodegeneration largely, and synaptic damage in AD. However, there is no investigation of the association between plasma NFL and white matter microstructure integrity. we have investigated the cross-sectional associations of plasma NFL, CSF tau, p tau, and Aβ with white matter microstructural changes as measured by DTI in 92 mild cognitive impairment (MCI) participants. We investigated potential correlations of the DTI values of each region of the MNI atlas, with plasma NFL, CSF total tau, CSF p tau, and as well as CSF Aβ, separately using a partial correlation model controlled for the effect of age, sex and APOE ε4 genotype. Our findings revealed a significant correlation between plasma and CSF biomarkers with altered white matter microstructural changes in widespread brain regions. Plasma NFL has a negative correlation with FA and positive correlation with RD, AD, and MD values in different regions. Plasma NFL promises to be an early biomarker of microstructural changes in MCI and for MCI progression to AD.

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Plasma p tau 181 levels is associated with white matter microstructural changes in across the Alzheimer’s disease stages

10.21203/rs.3.rs-115316/v2 ◽

2020 ◽

Author(s):

Fardin Nabizadeh ◽

Seyed Behnamedin Jameie ◽

Saghar Khani ◽

Aida Rezaei ◽

Fatemeh Ranjbaran ◽

...

Keyword(s):

Alzheimer’S Disease ◽

Alzheimer's Disease ◽

White Matter ◽

Behavioral Problems ◽

Structural Changes ◽

Cognitive Impairments ◽

Mean Diffusivity ◽

Region Of Interest ◽

Diagnostic Procedures ◽

Microstructural Changes

Abstract Alzheimer’s Disease (AD) is characterized by cognitive impairments and memory difficulties, which hinder daily activities and lead to personal and behavioral problems. In recent years, blood-based biomarkers like plasma phosphorylated tau protein at threonine 181 (p tau 181) emerged as new tools and showed sufficient power in detecting AD patients from healthy people. Here we investigate the correlation between p tau 181 and white matter microstructural changes in AD. We add 41 patients diagnosed with Alzheimer’s, 119 patients with mild cognitive impairments and 43 healthy controls with baseline plasma p tau 181 level and DTI values for each region of interest from the ADNI database. The analysis revealed that the plasma level of p tau 181 could predict changes of MD (Mean Diffusivity), RD (Radial Diffusivity), DA (Axial Diffusivity) and FA (Fractional Anisotropy) parameters in widespread regions and there is a significant association between white matter pathway alteration in different regions and p tau 181 plasma measurements within each group. In conclusion, our findings showed that plasma p tau 181 levels are associated with cellular and molecular changes in AD, which enhance the biomarkers for diagnostic procedures and support the application of plasma p tau 181 as a biomarker for white matter changes and neurodegeneration. Longitudinal studies are also necessary for proving the efficacy of these biomarkers and predicting the role in structural changes.

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Plasma p tau 181 are associated with white matter microstructural changes in Alzheimer’s disease

10.21203/rs.3.rs-115316/v1 ◽

2020 ◽

Author(s):

Fardin Nabizadeh ◽

Seyed Behnamedin Jameie ◽

Saghar Khani ◽

Aida Rezaei ◽

Niloofar Deravi

Keyword(s):

Alzheimer’S Disease ◽

Alzheimer's Disease ◽

White Matter ◽

Structural Changes ◽

Cognitive Impairments ◽

Mean Diffusivity ◽

Region Of Interest ◽

Diagnostic Procedures ◽

Microstructural Changes ◽

Sufficient Power

Abstract Alzheimer’s Disease (AD) is characterized by cognitive impairments and memory difficulties, which cause daily activities, personal and behavioural problems. In recent years blood-based biomarkers like plasma phosphorylated tau protein at threonine 181 (p tau 181) emerged as new tools and showed a sufficient power in detecting AD patients from healthy people. Here we investigate the correlation between p tau 181 and white matter microstructural changes in AD. We add 41 Alzheimer diagnosed patients, 155 participants with mild cognitive impairments and 43 healthy controls with baseline plasma p tau 181 level and DTI values for each region of interest from the ADNI database. The analysis revealed that the plasma level of p tau 181 could predict changes of MD( Mean Diffusivity), RD(Radial Diffusivity), DA(Axial Diffusivity) and FA(Fractional Anisotropy) parameters in widespread regions and there is a significant association between white matter pathways alteration in different regions and p tau 181 plasma measurement within each group. In conclusion, our findings showed that plasma p tau 181 levels are associated with cellular and molecular changes in AD, which enhance this biomarker's for diagnostic procedures and support the application of plasma p tau 181 as a biomarker for white matter changes and neurodegeneration. Longitudinal studies are also necessary to prove the efficacy of these biomarkers and predicting role in structural changes.

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Plasma neurofilament light is associated with white matter damage in Alzheimer's disease

10.21203/rs.3.rs-115308/v2 ◽

2020 ◽

Author(s):

Fardin Nabizadeh ◽

Mohammad Balabandian ◽

Mohammad Reza Rostami ◽

Samuel Berchi Kankam ◽

Fetemeh Ranjbaran ◽

...

Keyword(s):

Alzheimer’S Disease ◽

Alzheimer's Disease ◽

White Matter ◽

Diffusion Tensor ◽

Amyloid Β ◽

Brain Regions ◽

Csf Biomarkers ◽

Cross Sectional ◽

Neurofilament Light ◽

Microstructural Changes

Abstract The most replicated blood biomarker for monitoring Alzheimer’s disease is neurofilament light (NFL). Recent evidence revealed that the plasma level of the NFL has a strong predictive value in cognitive decline and is elevated in AD patients. The Diffusion Tensor Imaging (DTI) is understood to reflect white matter disruption, neurodegeneration, and synaptic damage in AD. However, few investigations have been carried out on the association between plasma NFL and white matter microstructure integrity. We have investigated the cross-sectional associations of plasma NFL, CSF total tau, phosphorylated tau, and Amyloid β with white matter microstructural changes as measured by DTI in 92 mild cognitive impairment (MCI) participants. We investigated potential correlations of the DTI values of each region of the MNI atlas, with plasma NFL, separately using a partial correlation model controlled for the effect of age, sex, and APOE ε4 genotype. Our findings revealed a significant correlation between plasma and CSF biomarkers with altered white matter microstructural changes in widespread brain regions. Plasma NFL negatively correlates with FA and the positive correlation with RD, DA, and MD values in different regions. Our findings showed that plasma NFL is associated with white matter changes and AD-related features, including atrophy and hypometabolism. Plasma NFL promises to be an early biomarker of microstructural changes in MCI and MCI progression to AD.

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Plasma P-tau181 levels reflects white matter microstructural changes across Alzheimer’s disease progression

10.21203/rs.3.rs-115316/v3 ◽

2021 ◽

Author(s):

Fardin Nabizadeh ◽

Seyed Behnamedin Jameie ◽

Saghar Khani ◽

Aida Rezaei ◽

Fatemeh Ranjbaran ◽

...

Keyword(s):

Alzheimer’S Disease ◽

Alzheimer's Disease ◽

White Matter ◽

Behavioral Problems ◽

Structural Changes ◽

Diffusion Tensor ◽

Cognitive Impairments ◽

Mean Diffusivity ◽

Diagnostic Procedures ◽

Microstructural Changes

Abstract Alzheimer’s Disease (AD) is characterized by cognitive impairments and memory difficulties that hinder daily activities and lead to personal and behavioral problems. Plasma hyperphosphorylated tau protein at threonine 181 (p-tau181), a blood-based biomarker, has recently emerged as a new tool with sufficient sensitivity for distinguishing AD patients from healthy people. We herein investigated the association of plasma P-tau181 and white matter (WM) microstructural changes in AD. We examined data from a large prospective cohort of elderly individuals participating in the Alzheimer’s Disease Neuroimaging Initiative (ADNI) which covers a wide clinical spectrum from normal cognition to AD dementia with measurements of plasma P-tau181 and imaging findings at baseline. A subset of 41 patients with AD, 119 patients with mild cognitive impairments (MCI), and 43 healthy controls (HC) were included in the study, all of whom had baseline blood P-tau181 levels and had also undergone Diffusion Tensor Imaging (DTI). The analysis revealed that the plasma level of P-tau181 have positive correlation with changes in Mean Diffusivity (MD), Radial Diffusivity (RD), and Axial Diffusivity (AxD), but a negative with Fractional Anisotropy (FA) parameters in WM regions of all participants. There is also a significant association between WM microstructural changes in different regions and P-tau181 plasma measurements within each MCI, HC and AD group. In conclusion, our findings clarified that plasma P-tau181 levels are associated with changes in WM integrity in AD. P-tau181 could improve the accuracy of diagnostic procedures and support the application of blood-based biomarkers to diagnose WM neurodegeneration. Longitudinal clinical studies are also needed to demonstrate the efficacy of the P-tau181 biomarker and predict its role in structural changes.

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