TY - JOUR
T1 - Loss of white matter integrity reflects tau accumulation in Alzheimer disease defined regions
AU - Strain, Jeremy F.
AU - Smith, Robert X.
AU - Beaumont, Helen
AU - Roe, Catherine M.
AU - Gordon, Brian A.
AU - Mishra, Shruti
AU - Adeyemo, Babatunde
AU - Christensen, Jon J.
AU - Su, Yi
AU - Morris, John C.
AU - Benzinger, Tammie L.S.
AU - Ances, Beau M.
N1 - Funding Information:
This study was funded by NIH grants R01NR012907, R01NR012657, R01NR014449, P50AG05681, P01AG003991, P01AG026276, P30NS048056, UL1TR000448, R01AG04343404, and National Science Foundation grant DMS1300280. Funding was also provided by the Charles F. and Joanne Knight Alzheimer’s Research Initiative, the Hope Center for Neurological Disorders, with generous support from the Fred Simmons and Olga Mohan Fund, the Paula and Rodger O. Riney Fund, and the Daniel J Brennan MD Fund. Avid Radiopharmaceuticals (a wholly owned subsidiary of Eli Lilly) provided AV-45 doses and partial financial support for the AV-45 sessions. Avid Radiopharmaceuticals also provided the precursor for AV-1451 and radiopharmaceutical chemistry and technology to the Washington University Investigational New Drug, under which this study was performed.
Funding Information:
This study was funded by NIH grants R01NR012907, R01NR012657, R01NR014449, P50AG05681, P01AG003991, P01AG026276, P30NS048056, UL1TR000448, R01AG04343404, and National Science Foundation grant DMS1300280. Funding was also provided by the Charles F. and Joanne Knight Alzheimer's Research Initiative, the Hope Center for Neurological Disorders, with generous support from the Fred Simmons and Olga Mohan Fund, the Paula and Rodger O. Riney Fund, and the Daniel J Brennan MD Fund. Avid Radiopharmaceuticals (a wholly owned subsidiary of Eli Lilly) provided AV-45 doses and partial financial support for the AV-45 sessions. Avid Radiopharmaceuticals also provided the precursor for AV-1451 and radiopharmaceutical chemistry and technology to the Washington University Investigational New Drug, under which this study was performed.
Publisher Copyright:
© 2018 American Academy of Neurology
PY - 2018/7/24
Y1 - 2018/7/24
N2 - Objective White matter (WM) projections were assessed from Alzheimer disease (AD) gray matter regions associated with β-amyloid (Aβ), tau, or neurodegeneration to ascertain relationship between WM structural integrity with Aβ and/or tau deposition. Methods Participants underwent diffusion tensor imaging (DTI), PET Aβ ([18F]AV-45 [florbetapir]), and PET tau ([18F]AV-1451 [flortaucipir]) imaging. Probabilistic WM summary and individual tracts were created from either a composite or individual gray matter seed regions derived from Aβ, tau, and neurodegeneration. Linear regressions were performed for Aβ, age, tau and WM hyperintensities (WMH) to predict mean diffusivity (MD) or fractional anisotropy (FA) from the corresponding WM summaries or tracts. Results Our cohort was composed of 59 cognitively normal participants and 10 cognitively impaired individuals. Aβ was not associated with DTI metrics in WM summary or individual tracts. Age and WMH strongly predicted MD and FA in several WM regions, with tau a significant predictor of MD only in the anterior temporal WM. Conclusion Tau, not Aβ, was associated with changes in anterior temporal WM integrity. WMH, a proxy for vascular damage, was strongly associated with axonal damage, but tau independently contributed to the model, suggesting an additional degenerative mechanism within tracts projecting from regions vulnerable to AD pathology. WM decline was associated with early tau accumulation, and further decline may reflect tau propagation in more advanced stages of AD.
AB - Objective White matter (WM) projections were assessed from Alzheimer disease (AD) gray matter regions associated with β-amyloid (Aβ), tau, or neurodegeneration to ascertain relationship between WM structural integrity with Aβ and/or tau deposition. Methods Participants underwent diffusion tensor imaging (DTI), PET Aβ ([18F]AV-45 [florbetapir]), and PET tau ([18F]AV-1451 [flortaucipir]) imaging. Probabilistic WM summary and individual tracts were created from either a composite or individual gray matter seed regions derived from Aβ, tau, and neurodegeneration. Linear regressions were performed for Aβ, age, tau and WM hyperintensities (WMH) to predict mean diffusivity (MD) or fractional anisotropy (FA) from the corresponding WM summaries or tracts. Results Our cohort was composed of 59 cognitively normal participants and 10 cognitively impaired individuals. Aβ was not associated with DTI metrics in WM summary or individual tracts. Age and WMH strongly predicted MD and FA in several WM regions, with tau a significant predictor of MD only in the anterior temporal WM. Conclusion Tau, not Aβ, was associated with changes in anterior temporal WM integrity. WMH, a proxy for vascular damage, was strongly associated with axonal damage, but tau independently contributed to the model, suggesting an additional degenerative mechanism within tracts projecting from regions vulnerable to AD pathology. WM decline was associated with early tau accumulation, and further decline may reflect tau propagation in more advanced stages of AD.
UR - http://www.scopus.com/inward/record.url?scp=85054642696&partnerID=8YFLogxK
U2 - 10.1212/WNL.0000000000005864
DO - 10.1212/WNL.0000000000005864
M3 - Article
C2 - 29959265
AN - SCOPUS:85054642696
SN - 0028-3878
VL - 91
SP - E313-E318
JO - Neurology
JF - Neurology
IS - 4
ER -