Association between neurite metrics and tau/inflammatory pathology in Alzheimer's disease

Sone, Daichi; Shigemoto, Yoko; Ogawa, Masayo; Maikusa, Norihide; Okita, Kyoji; Takano, Harumasa; Kato, Koichi; Sato, Noriko

doi:10.1002/dad2.12125

Cited by 17 publications

(22 citation statements)

References 44 publications

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“…[50] Another study explored correlations between grey matter changes in neurite density and tau PET in sporadic AD. [51] Decreased neurite density was associated regionally with tau deposition which is itself associated with neuroinflammation. Another, more recent study suggested FISO could provide an surrogate measure of tau deposition in AD.…”

Section: Discussionmentioning

confidence: 99%

Imaging synaptic microstructure and synaptic loss in vivo in early Alzheimer’s Disease

Venkataraman

Bishop

Mansur

et al. 2021

Preprint

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1.ABSTRACTBackgroundSynaptic loss and neurite dystrophy are early events in Alzheimer’s Disease (AD). We aimed to characterise early synaptic microstructural changes in vivo.MethodsMRI neurite orientation dispersion and density imaging (NODDI) and diffusion tensor imaging (DTI) were used to image cortical microstructure in both sporadic, late onset, amyloid PET positive AD patients and healthy controls (total n = 28). We derived NODDI measures of grey matter extracellular free water (FISO), neurite density (NDI) and orientation dispersion (ODI), which provides an index of neurite branching and orientation, as well as more conventional DTI measures of fractional anisotropy (FA), mean/axial/radial diffusivity (MD, AD, RD, respectively). We also performed [11C]UCB-J PET, which provides a specific measure of the density of pre-synaptic vesicular protein SV2A. Both sets of measures were compared to regional brain volumes.ResultsThe AD patients showed expected relative decreases in regional brain volumes (range, -6 to - 23%) and regional [11C]UCB-J densities (range, -2 to -25%). Differences between AD and controls were greatest in the hippocampus. NODDI microstructural measures showed greater FISO (range, +26 to +44%) in AD, with little difference in NDI (range, -1 to +7%) and mild focal changes in ODI (range, -4 to +3%). Regionally greater FISO and lower [11C]UCB-J binding were correlated across grey matter in patients (most strongly in the caudate, r2 = 0.37, p = 0.001). FISO and DTI RD were strongly positively associated, particularly in the hippocampus (r2 = 0.98, p < 7.4 × 10−9). After 12-18 months we found a 5% increase in FISO in the temporal lobe, but little change across all ROIs in NDI and ODI. An exploratory analysis showed higher parietal lobe FISO was associated with lower language scores in people with AD.ConclusionsWe interpreted the increased extracellular free water as a possible consequence of glial activation. The dynamic range of disease-associated differences and the feasibility of measuring FISO on commercially available imaging systems makes it a potential surrogate for pathology related to synapse loss that could be used to support early-stage evaluations of novel therapeutics for AD.

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Section: Discussionmentioning

confidence: 99%

Imaging synaptic microstructure and synaptic loss in vivo in early Alzheimer’s Disease

Venkataraman

Bishop

Mansur

et al. 2021

Preprint

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“…In AD compared to healthy aging control, lower cortical ODI and NDI values have been shown in temporal and frontal lobes 19,20 . Reductions in cortical NDI were associated with impaired neuropsychological performance in AD patients 19–22 , and 18 F-THK5351 was shown to negatively correlate with ODI and NDI in gray matter in 11 C-PiB+ patients 23 . In line with the human in vivo imaging studies, rodent in vivo imaging has shown that tau-mouse models have lower cortical and hippocampal NDI values than wild type mice, and NODDI metrics tracked histopathology better than DTI-derived measures 21 .…”

Section: Introductionmentioning

confidence: 91%

In Vivo Cortical Microstructure: A Proxy for Tauopathy and Cognitive impairment in the Elderly with and without MCI/Dementia

Anderson

Schifani

Nazeri

et al. 2021

Preprint

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Aggregation of hyperphosphorylated tau protein is currently one of the most reliable indicators of Alzheimer's pathology and cognitive impairment in older adults. However, it would be useful to have a non-invasive, accessible proxy measure that does not rely on Positron Emission Tomography (PET). We used data from multi-shell diffusion-weighted imaging (DWI) to assess indices from the Neurite Orientation Dispersion and Density Imaging (NODDI) model to determine possible proxies for tau and relationship with cognitive impairment. After controlling for age, sex, and the time difference between the scan acquisitions (DWI vs. PET), we used multiple factor analysis (MFA) to assess the fit between NODDI indices (orientation dispersion [ODI], neurite density [NDI], and free-water [fISO]), cortical thickness, and tau binding (via PET). We used data from 80 participants from the ADNI-3 sample who had a multi-shell DWI and an [18F]AV-1451 (tau) PET scan. Of these 80, 49 individuals were considered cognitively normal older adults (age ~74 years), 26 individuals had a diagnosis of mild cognitive impairment (age ~75 years), and five individuals had Alzheimer's dementia (age ~78 years). fISO and tau shared a large amount of spatial overlap, and both strongly correlated with the first MFA dimension. Macrostructural features (such as cortical thickness and subcortical volume) introduced in a follow-up analysis were less related to this first MFA dimension than fISO and eight percent less than tau. Subsequent mediation analyses demonstrated that fISO mediated the relationship between cortical thickness and tau, explaining all of the variance. Microstructural features derived from advanced DWI acquisitions such as fISO may be useful proxies for tau. Cortical fISO, rather than cortical thickness, may represent the impact of tau on the brain (and, by extension, cognition).

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“…Recently, Sone et al, investigated the association between PET metrics using the novel tracer 18 F-THK5351 and NODDI metrics in AlzD-spectrum participants and controls [ 83 ]. 18 F-THK5351 was employed as a tracer of tau pathology and astrogliosis-related neuroinflammation [ 84 , 85 ].…”

Section: Applications Of Advanced Diffusion Mri Techniques In Neurodegenerative Diseasesmentioning

confidence: 99%

“…Color bars denote statistically significant T-values ranging from minimum to maximum. Abbreviations: AD-S, Alzheimer’s disease spectrum; NDI, neurite density index; NODDI, neurite orientation dispersion and density imaging; ODI, orientation dispersion index; PET, positron emission tomography (adapted and reproduced with permission from Sone et al [ 83 ]).…”

Section: Figurementioning

confidence: 99%

Diffusion Magnetic Resonance Imaging-Based Biomarkers for Neurodegenerative Diseases

Kamagata

Andica

Kato

et al. 2021

IJMS

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There has been an increasing prevalence of neurodegenerative diseases with the rapid increase in aging societies worldwide. Biomarkers that can be used to detect pathological changes before the development of severe neuronal loss and consequently facilitate early intervention with disease-modifying therapeutic modalities are therefore urgently needed. Diffusion magnetic resonance imaging (MRI) is a promising tool that can be used to infer microstructural characteristics of the brain, such as microstructural integrity and complexity, as well as axonal density, order, and myelination, through the utilization of water molecules that are diffused within the tissue, with displacement at the micron scale. Diffusion tensor imaging is the most commonly used diffusion MRI technique to assess the pathophysiology of neurodegenerative diseases. However, diffusion tensor imaging has several limitations, and new technologies, including neurite orientation dispersion and density imaging, diffusion kurtosis imaging, and free-water imaging, have been recently developed as approaches to overcome these constraints. This review provides an overview of these technologies and their potential as biomarkers for the early diagnosis and disease progression of major neurodegenerative diseases.

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Association between neurite metrics and tau/inflammatory pathology in Alzheimer's disease

Cited by 17 publications

References 44 publications

Imaging synaptic microstructure and synaptic loss in vivo in early Alzheimer’s Disease

Imaging synaptic microstructure and synaptic loss in vivo in early Alzheimer’s Disease

In Vivo Cortical Microstructure: A Proxy for Tauopathy and Cognitive impairment in the Elderly with and without MCI/Dementia

Diffusion Magnetic Resonance Imaging-Based Biomarkers for Neurodegenerative Diseases

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