Hypoperfusion Precedes Tau Deposition in the Entorhinal Cortex: A Retrospective Evaluation of ADNI-2 Data
1
조회
0
다운로드
0
인용
0
참고문헌
키워드
초록
Background and Purpose Tau deposition in the entorhinal cortex is the earliest pathological feature of Alzheimer’s disease (AD). However, this feature has also been observed in cognitively normal (CN) individuals and those with mild cognitive impairment (MCI). The precise pathophysiology for the development of tau deposition remains unclear. We hypothesized that reduced cerebral perfusion is associated with the development of tau deposition. Methods A subset of the Alzheimer’s Disease Neuroimaging Initiative data set was utilized. Included patients had undergone arterial spin labeling perfusion MRI along with [18F]flortaucipir tau PET at baseline, within 1 year of the MRI, and a follow-up at 6 years. The association between baseline cerebral blood flow (CBF) and the baseline and 6-year tau PET was assessed. Univariate and multivariate linear modeling was performed, with p<0.05 indicating significance. Results Significant differences were found in the CBF between patients with AD and MCI, and CN individuals in the left entorhinal cortex (p=0.013), but not in the right entorhinal cortex (p=0.076). The difference in maximum standardized uptake value ratio between 6 years and baseline was significantly and inversely associated with the baseline mean CBF (p=0.042, R2=0.54) in the left entorhinal cortex but not the right entorhinal cortex. Linear modeling demonstrated that CBF predicted 6-year tau deposition (p=0.015, R2=0.11). Conclusions The results of this study suggest that a reduction in CBF at the entorhinal cortex precedes tau deposition. Further work is needed to understand the mechanism underlying tau deposition in aging and disease.
Abstract
Background and Purpose Tau deposition in the entorhinal cortex is the earliest pathological feature of Alzheimer’s disease (AD). However, this feature has also been observed in cognitively normal (CN) individuals and those with mild cognitive impairment (MCI). The precise pathophysiology for the development of tau deposition remains unclear. We hypothesized that reduced cerebral perfusion is associated with the development of tau deposition. Methods A subset of the Alzheimer’s Disease Neuroimaging Initiative data set was utilized. Included patients had undergone arterial spin labeling perfusion MRI along with [18F]flortaucipir tau PET at baseline, within 1 year of the MRI, and a follow-up at 6 years. The association between baseline cerebral blood flow (CBF) and the baseline and 6-year tau PET was assessed. Univariate and multivariate linear modeling was performed, with p<0.05 indicating significance. Results Significant differences were found in the CBF between patients with AD and MCI, and CN individuals in the left entorhinal cortex (p=0.013), but not in the right entorhinal cortex (p=0.076). The difference in maximum standardized uptake value ratio between 6 years and baseline was significantly and inversely associated with the baseline mean CBF (p=0.042, R2=0.54) in the left entorhinal cortex but not the right entorhinal cortex. Linear modeling demonstrated that CBF predicted 6-year tau deposition (p=0.015, R2=0.11). Conclusions The results of this study suggest that a reduction in CBF at the entorhinal cortex precedes tau deposition. Further work is needed to understand the mechanism underlying tau deposition in aging and disease.
참고문헌 (41)
- Alzheimer’s Association, "2019 Alzheimer’s disease facts and figures", Alzheimers Dement, 15, pp.321~387 (2019)
- Deb A, "Direct and indirect cost of managing alzheimer’s disease and related dementias in the United States", Expert Rev Pharmacoecon Outcomes Res, 17, pp.189~202 (2017)
- Serrano-Pozo A, "Neuropathological alterations in Alzheimer disease", Cold Spring Harb Perspect Med, 1, pp.a006189~ (2011)
- Blennow K, "Biomarkers for Alzheimer’s disease : current status and prospects for the future", J Intern Med, 284, pp.643~663 (2018)
- DeTure MA, "The neuropathological diagnosis of Alzheimer’s disease", Mol Neurodegener, 14, pp.32~ (2019)
- Kapadia A, "Intersection between sleep and neurovascular coupling as the driving pathophysiology of Alzheimer’s disease", Med Hypotheses, 144, pp.110283~ (2020)
- Ziontz J, "Tau pathology in cognitively normal older adults", Alzheimers Dement(Amst), 11, pp.637~645 (2019)
- Dani M, "Tau aggregation correlates with amyloid deposition in both mild cognitive impairment and Alzheimer’s disease subjects", J Alzheimers Dis, 70, pp.455~465 (2019)
- Maass A, "Entorhinal tau pathology, episodic memory decline, and neurodegeneration in aging", J Neurosci, 38, pp.530~543 (2018)
- Harrison TM, "Tau deposition is associated with functional isolation of the hippocampus in aging", Nat Commun, 10, pp.4900~ (2019)
- flortaucipir with postmortem Alzheimer disease tau pathology, "JAMA Neurol", 2019, 310~317
- Pontecorvo MJ, "Comparison of regional flortaucipir PET with quantitative tau immunohistochemistry in three subjects with Alzheimer’s disease pathology : a clinicopathological study", EJNMMI Res, 10, pp.65~ (2020)
- Zhou G, "Impaired cerebral autoregulation in Alzheimer’s disease : a transcranial Doppler study", J Alzheimers Dis, 72, pp.623~631 (2019)
- van Beek AH, "Oscillations in cerebral blood flow and cortical oxygenation in Alzheimer’s disease", Neurobiol Aging, 33, pp.428~ (2012)
- Qiu L, "Chronic cerebral hypoperfusion enhances tau hyperphosphorylation and reduces autophagy in Alzheimer’s disease mice", Sci Rep, 6, pp.23964~ (2016)
- Zhu J, "Intracranial artery stenosis and progression from mild cognitive impairment to Alzheimer disease", Neurology, 82, pp.842~849 (2014)
- Rubinski A, "Lower cerebral perfusion is associated with tau-PET in the entorhinal cortex across the Alzheimer’s continuum", Neurobiol Aging, 102, pp.111~118 (2021)
- Petersen RC, "Alzheimer’s Disease Neuroimaging Initiative(ADNI) : clinical characterization", Neurology, 74, pp.201~209 (2010)
- Aisen PS, "Alzheimer’s Disease Neuroimaging Initiative 2 clinical core : progress and plans", Alzheimers Dement, 11, pp.734~739 (2015)
- Luh WM, "QUIPSS II with thin-slice TI1 periodic saturation : a method for improving accuracy of quantitative perfusion imaging using pulsed arterial spin labeling", Magn Reson Med, 41, pp.1246~1254 (1999)
- Zhao Q, "Quantitative 18F-AV1451 brain tau PET imaging in cognitively normal older adults, mild cognitive impairment, and Alzheimer’s disease patients", Front Neurol, 10, pp.486~ (2019)
- Drzezga A, "Cerebral glucose metabolism in patients with AD and different APOE genotypes", Neurology, 64, pp.102~107 (2005)
- Matsuda H, "Automatic voxel-based morphometry of structural MRI by SPM8 plus diffeomorphic anatomic registration through exponentiated lie algebra improves the diagnosis of probable Alzheimer disease", AJNR Am J Neuroradiol, 33, pp.1109~1114 (2012)
- Tohka J, "Deconvolution-based partial volume correction in Raclopride-PET and Monte Carlo comparison to MR-based method", Neuroimage, 39, pp.1570~1584 (2008)
- Paranjpe MD, "The effect of ApoE ε4 on longitudinal brain region-specific glucose metabolism in patients with mild cognitive impairment : a FDG-PET study", Neuroimage Clin, 22, pp.101795~ (2019)
- Benjamini Y, "Controlling the false discovery rate : a practical and powerful approach to multiple testing", J R Stat Soc Series B Stat Methodol, 57, pp.289~300 (1995)
- McDonald JH, "Handbook of Biological Statistics", pp.317~ (2009), Sparky House Publishing
- Braak H, "Neuropathological stageing of Alzheimer-related changes", Acta Neuropathol, 82, pp.239~259 (1991)
- van Rossum IA, "Injury markers but not amyloid markers are associated with rapid progression from mild cognitive impairment to dementia in Alzheimer’s disease", J Alzheimers Dis, 29, pp.319~327 (2012)
- Arriagada PV, "Neurofibrillary tangles but not senile plaques parallel duration and severity of Alzheimer’s disease", Neurology, 42(3 Pt 1), pp.631~639 (1992)
- Rentz DM, "Cognition, reserve, and amyloid deposition in normal aging", Ann Neurol, 67, pp.353~364 (2010)
- Mukaetova-Ladinska EB, "Alterations in tau protein metabolism during normal aging", Dementia, 7, pp.95~103 (1996)
- Nelson PT, "Correlation of Alzheimer disease neuropathologic changes with cognitive status : a review of the literature", J Neuropathol Exp Neurol, 71, pp.362~381 (2012)
- Brier MR, "Tau and Aβ imaging, CSF measures, and cognition in Alzheimer’s disease", Sci Transl Med, 8, pp.338~ (2016)
- Maass A, "Comparison of multiple tau-PET measures as biomarkers in aging and Alzheimer’s disease", Neuroimage, 157, pp.448~463 (2017)
- Pontecorvo MJ, "Relationships between flortaucipir PET tau binding and amyloid burden, clinical diagnosis, age and cognition", Brain, 140, pp.748~763 (2017)
- Marks SM, "Tau and β-amyloid are associated with medial temporal lobe structure, function, and memory encoding in normal aging", J Neurosci, 37, pp.3192~3201 (2017)
- Ossenkoppele R, "Tau PET patterns mirror clinical and neuroanatomical variability in Alzheimer’s disease", Brain, 139(Pt 5), pp.1551~1567 (2016)
- Laing KK, "Cerebrovascular disease promotes tau pathology in Alzheimer’s disease", Brain Commun, 2, pp.fcaa132~ (2020)
- Visser D, "Tau pathology and relative cerebral blood flow are independently associated with cognition in Alzheimer’s disease", Eur J Nucl Med Mol Imaging, 47, pp.3165~3175 (2020)
- Albrecht D, "Associations between vascular function and tau PET are associated with global cognition and amyloid", J Neurosci, 40, pp.8573~8586 (2020)