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Alzheimers Dement
December 2024
Laboratory of Clinical Investigation, National Institute on Aging, Intramural Research Program, Baltimore, MD, USA.
Background: Neurite degeneration is increasingly suspected to represent a causal feature of mild cognitive impairment (MCI) and Alzheimer's disease (AD). Therefore, sensitive and specific imaging biomarkers of neuronal degeneration are needed to elucidate the mechanisms underlying cognitive impairment in MCI and AD. However, the recently developed Neurite Orientation Dispersion and Density Imaging (NODDI) MRI technique, used to measure the neurite density index (NDI), has some limitations.
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Alzheimers Dement
December 2024
Michigan Alzheimer's Disease Research Center, Ann Arbor, MI, USA.
Background: Diffusion magnetic resonance imaging (dMRI) permits characterizing differences in white matter microstructure associated with amnestic mild cognitive impairment (aMCI) and Alzheimer's dementia (AD). However, most dMRI measures aggregate signals across multiple axonal fiber populations with varying spatial orientations, which limits the sensitivity and specificity of clinical diagnosis. To overcome this shortcoming, we estimated fiber density (FD) measures, independently from crossing fiber populations, and extracellular cerebral spinal fluid (CSF).
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Alzheimers Dement
December 2024
Laboratory of Clinical Investigation, National Institute on Aging, Intramural Research Program, Baltimore, MD, USA.
Background: Neuroimaging-based evidence suggests that changes in cerebral tissue determinants, including axonal density and myelin content, are associated with aging and neurodegenerative diseases. While neuroimaging markers show strong association with physiological changes, direct validation of their specificity remains challenging. Histology provides useful information for validation, however, faces limitations including denaturation of the sample during preparation.
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Alzheimers Dement
December 2024
Munich Cluster for Systems Neurology (SyNergy), Munich, Bavaria, Germany.
Background: In Alzheimer's disease (AD), cortical tau aggregation is a strong predictor of cortical brain atrophy as shown by MRI and PET studies, particularly driving the degeneration of neuronal somata in the grey matter. However, tau's physiological role is to stabilize microtubules within axons in the brain's white matter (WM) pathways. Therefore, tau's white-to-grey-matter translocation and aggregation in neurofibrillary tangles close to neuronal somata may induce WM degeneration through destabilization of axonal microtubule integrity.
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Alzheimers Dement
December 2024
Douglas Mental Health University Institute, Montreal, QC, Canada.
White matter hyperintensities (WMHs) are frequently observed in ageing individuals, and have a higher prevalence in neurodegenerative disorders such as Alzheimer's disease. Ex-vivo assessments of the microstructural alterations within WMHs have reported heterogeneous tissue alterations, with demyelination, axonal loss, and inflammation presenting with various degrees of severity. There is a crucial need to better assess the severity of WMH microstructural alterations in vivo, in particular with the emergence of anti-amyloid immunotherapies and the associated risk of Amyloid Related Imaging Abnormalities (ARIAs) in individuals with comorbid vascular disease.
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