Associations in Alzheimer’s disease between intracranial vascular metrics from 4D‐flow MRI and β‐amyloid and tau PET

Cerebral blood flow, arterial pulsation, and vasomotion play important roles in the transport of waste metabolites out of the brain. Impaired vasomotion results in reduced driving force for the perivascular/glymphatic clearance of beta-amyloid. Noninvasive cerebrovascular characteristic features that potentially assess these transport mechanisms are mean blood flow (MBF) and pulsatility index (PI). In this study, 4D flow MRI was used to measure intra-cranial flow features, particularly MBF, PI, resistive index (RI) and cross-sectional area in patients with Alzheimer’s disease (AD), mild cognitive impairment and in age matched and younger cognitively healthy controls. Three-hundred fourteen subjects participated in this study. Volumetric, time-resolved phase contrast (PC) MRI data were used to quantify hemodynamic parameters from 11 vessel segments. Anatomical variants of the Circle of Willis were also cataloged. The AD population reported a statistically significant decrease in MBF and cross-sectional area, and also an increase in PI and RI compared to age matched cognitively healthy control subjects. The 4D flow MRI technique used in this study provides quantitative measurements of intracranial vessel geometry and the velocity of flow. Cerebrovascular characteristics features of vascular health such as pulsatility index can be extracted from the 4D flow MRI data.

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Intracranial vascular flow oscillations in Alzheimer’s disease from 4D flow MRI

NeuroImage Clinical ◽

10.1016/j.nicl.2020.102379 ◽

2020 ◽

Vol 28 ◽

pp. 102379

Author(s):

Leonardo A. Rivera-Rivera ◽

Karly A. Cody ◽

David Rutkowski ◽

Paul Cary ◽

Laura Eisenmenger ◽

...

Keyword(s):

Alzheimer’S Disease ◽

Alzheimer's Disease ◽

4D Flow Mri ◽

4D Flow ◽

Vascular Flow ◽

Flow Mri ◽

Flow Oscillations

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Assessment of intracranial vascular flow oscillations in Alzheimer’s disease using real time 4D flow MRI

Alzheimer s & Dementia ◽

10.1002/alz.044536 ◽

2020 ◽

Vol 16 (S4) ◽

Author(s):

Leonardo A Rivera ◽

Laura Eisenmenger ◽

Paul Cary ◽

Sterling C. Johnson ◽

Kevin M Johnson

Keyword(s):

Alzheimer’S Disease ◽

Alzheimer's Disease ◽

Real Time ◽

4D Flow Mri ◽

4D Flow ◽

Vascular Flow ◽

Flow Mri ◽

Flow Oscillations

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Soluble P-tau217 reflects amyloid and tau pathology and mediates the association of amyloid with tau

10.21203/rs.3.rs-101153/v2 ◽

2021 ◽

Author(s):

Niklas Mattsson-Carlgren ◽

Shorena Janelidze ◽

Randall Bateman ◽

Ruben Smith ◽

Erik Stomrud ◽

...

Keyword(s):

Alzheimer’S Disease ◽

Alzheimer's Disease ◽

Medial Temporal Lobe ◽

Amyloid Plaques ◽

Amyloid Plaque ◽

Amyloid Pet ◽

Tau Pathology ◽

Β Amyloid ◽

Tau Pet ◽

Disease Stages

Abstract Alzheimer’s disease is characterized by β-amyloid plaques and tau tangles. Plasma levels of phospho-tau217 (P-tau217) accurately differentiate Alzheimer’s disease dementia from other dementias, but it is unclear to what degree this reflects β-amyloid plaque accumulation, tau tangle accumulation, or both. In a cohort with post-mortem neuropathological data (N=88), both plaque and tangle density contributed independently to higher P-tau217. Several findings were replicated in a cohort with PET imaging (“BioFINDER-2”, N=426), where β-amyloid and tau PET were independently associated to P-tau217. P-tau217 correlated with β-amyloid PET (but not tau PET) in early disease stages, and with both β-amyloid and (more strongly) tau PET in late disease stages. Finally, P-tau217 mediated the association between β-amyloid and tau in both cohorts, especially for tau outside of the medial temporal lobe. These findings support the hypothesis that plasma P-tau217 is increased by both β-amyloid plaques and tau tangles and is congruent with the hypothesis that P-tau is involved in β-amyloid-dependent formation of neocortical tau tangles.

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Changes in intracranial venous blood flow and pulsatility in Alzheimer’s disease: A 4D flow MRI study

Journal of Cerebral Blood Flow & Metabolism ◽

10.1177/0271678x16661340 ◽

2016 ◽

Vol 37 (6) ◽

pp. 2149-2158 ◽

Cited By ~ 27

Author(s):

Leonardo A Rivera-Rivera ◽

Tilman Schubert ◽

Patrick Turski ◽

Kevin M Johnson ◽

Sara E Berman ◽

...

Keyword(s):

Alzheimer’S Disease ◽

Alzheimer's Disease ◽

Blood Flow ◽

Middle Cerebral Artery ◽

Cerebral Artery ◽

Peak Flow ◽

Superior Sagittal Sinus ◽

4D Flow ◽

Sagittal Sinus ◽

Flow Mri

Cerebral blood flow, arterial pulsation, and vasomotion may be important indicators of cerebrovascular health in aging and diseases of aging such as Alzheimer’s disease. Noninvasive markers that assess these characteristics may be helpful in the study of co-occurrence of these diseases and potential additive and interacting effects. In this study, 4D flow MRI was used to measure intra-cranial flow features with cardiac-gated phase contrast MRI in cranial arteries and veins. Mean blood flow and pulsatility index as well as the transit time of the peak flow from the middle cerebral artery to the superior sagittal sinus were measured in a total of 104 subjects comprising of four groups: (a) subjects with Alzheimer’s disease, (b) age-matched controls, (c) subjects with mild cognitive impairment, and (d) a group of late middle-aged with parental history of sporadic Alzheimer’s disease. The Alzheimer’s disease group exhibited: a significant decrease in mean blood flow in the superior sagittal sinus, transverse sinus, middle cerebral artery, and internal carotid arteries; a significant decrease of the peak and end diastolic blood flow in the middle cerebral artery and superior sagittal sinus; a faster transmission of peak flow from the middle cerebral artery to the superior sagittal sinus and increased pulsatility index along the carotid siphon.

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Prospective longitudinal atrophy in Alzheimer’s disease correlates with the intensity and topography of baseline tau-PET

Science Translational Medicine ◽

10.1126/scitranslmed.aau5732 ◽

2020 ◽

Vol 12 (524) ◽

pp. eaau5732 ◽

Cited By ~ 49

Author(s):

Renaud La Joie ◽

Adrienne V. Visani ◽

Suzanne L. Baker ◽

Jesse A. Brown ◽

Viktoriya Bourakova ◽

...

Keyword(s):

Alzheimer’S Disease ◽

Alzheimer's Disease ◽

Amyloid Pet ◽

Specific Distribution ◽

Positron Emission ◽

Pet Radiotracers ◽

Β Amyloid ◽

Tau Pet ◽

Prospective Longitudinal

β-Amyloid plaques and tau-containing neurofibrillary tangles are the two neuropathological hallmarks of Alzheimer’s disease (AD) and are thought to play crucial roles in a neurodegenerative cascade leading to dementia. Both lesions can now be visualized in vivo using positron emission tomography (PET) radiotracers, opening new opportunities to study disease mechanisms and improve patients’ diagnostic and prognostic evaluation. In a group of 32 patients at early symptomatic AD stages, we tested whether β-amyloid and tau-PET could predict subsequent brain atrophy measured using longitudinal magnetic resonance imaging acquired at the time of PET and 15 months later. Quantitative analyses showed that the global intensity of tau-PET, but not β-amyloid–PET, signal predicted the rate of subsequent atrophy, independent of baseline cortical thickness. Additional investigations demonstrated that the specific distribution of tau-PET signal was a strong indicator of the topography of future atrophy at the single patient level and that the relationship between baseline tau-PET and subsequent atrophy was particularly strong in younger patients. These data support disease models in which tau pathology is a major driver of local neurodegeneration and highlight the relevance of tau-PET as a precision medicine tool to help predict individual patient’s progression and design future clinical trials.

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Soluble P-tau217 reflects both amyloid and tau pathology in the human brain and mediates the association of amyloid with neocortical tau

10.21203/rs.3.rs-101153/v1 ◽

2020 ◽

Author(s):

Niklas Mattsson-Carlgren ◽

Shorena Janelidze ◽

Randall Bateman ◽

Ruben Smith ◽

Erik Stomrud ◽

...

Keyword(s):

Alzheimer’S Disease ◽

Alzheimer's Disease ◽

Medial Temporal Lobe ◽

Amyloid Plaques ◽

Amyloid Plaque ◽

Amyloid Pet ◽

Tau Pathology ◽

Β Amyloid ◽

Tau Pet ◽

Disease Stages

Abstract Alzheimer’s disease is characterized by β-amyloid plaques and tau tangles. Plasma levels of phospho-tau217 (P-tau217) accurately differentiate Alzheimer’s disease dementia from other dementias, but it is unclear to what degree this reflects β-amyloid plaque accumulation, tau tangle accumulation, or both. In a cohort with post-mortem neuropathological data (N=88), both plaque and tangle density contributed independently to higher P-tau217. Several findings were replicated in a cohort with PET imaging (“BioFINDER-2”, N=426), where β-amyloid and tau PET were independently associated to P-tau217. P-tau217 correlated with β-amyloid PET (but not tau PET) in early disease stages, and with both β-amyloid and (more strongly) tau PET in late disease stages. Finally, P-tau217 mediated the association between β-amyloid and tau in both cohorts, especially for tau outside of the medial temporal lobe. These findings support the hypothesis that plasma P-tau217 is increased by both β-amyloid plaques and tau tangles and is congruent with the hypothesis that P-tau is involved in β-amyloid-dependent formation of neocortical tau tangles.

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Staging tau pathology with tau PET in Alzheimer’s disease: a longitudinal study

Translational Psychiatry ◽

10.1038/s41398-021-01602-5 ◽

2021 ◽

Vol 11 (1) ◽

Author(s):

Shi-Dong Chen ◽

Jia-Ying Lu ◽

Hong-Qi Li ◽

Yu-Xiang Yang ◽

Jie-Hui Jiang ◽

...

Keyword(s):

Alzheimer’S Disease ◽

Alzheimer's Disease ◽

Cognitive Decline ◽

Tau Pathology ◽

Clinical Progression ◽

Mixed Effect ◽

Spreading Pattern ◽

Β Amyloid ◽

Tau Pet ◽

Stage 1

AbstractA biological research framework to define Alzheimer’ disease with dichotomized biomarker measurement was proposed by National Institute on Aging–Alzheimer’s Association (NIA–AA). However, it cannot characterize the hierarchy spreading pattern of tau pathology. To reflect in vivo tau progression using biomarker, we constructed a refined topographic 18F-AV-1451 tau PET staging scheme with longitudinal clinical validation. Seven hundred and thirty-four participants with baseline 18F-AV-1451 tau PET (baseline age 73.9 ± 7.7 years, 375 female) were stratified into five stages by a topographic PET staging scheme. Cognitive trajectories and clinical progression were compared across stages with or without further dichotomy of amyloid status, using linear mixed-effect models and Cox proportional hazard models. Significant cognitive decline was first observed in stage 1 when tau levels only increased in transentorhinal regions. Rates of cognitive decline and clinical progression accelerated from stage 2 to stage 3 and stage 4. Higher stages were also associated with greater CSF phosphorylated tau and total tau concentrations from stage 1. Abnormal tau accumulation did not appear with normal β-amyloid in neocortical regions but prompt cognitive decline by interacting with β-amyloid in temporal regions. Highly accumulated tau in temporal regions independently led to cognitive deterioration. Topographic PET staging scheme have potentials in early diagnosis, predicting disease progression, and studying disease mechanism. Characteristic tau spreading pattern in Alzheimer’s disease could be illustrated with biomarker measurement under NIA–AA framework. Clinical–neuroimaging–neuropathological studies in other cohorts are needed to validate these findings.

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