Cortical and Subcortical Changes in Alzheimer's Disease: A Longitudinal and Quantitative MRI Study

Su, Li; Blamire, Andrew M.; Watson, Rosie; He, Jiabao; Aribisala, Benjamin S.; O’Brien, John T.

doi:10.2174/1567205013666151116141416

Cited by 21 publications

(17 citation statements)

References 29 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…The inconsistencies between the previous and current studies could possibly be explained by group sizes with in the current study, the number of cases being larger. A significant reduction in the level of SIRT1 protein was observed in AD and this is most likely explained by the greater degree of cortical atrophy seen in AD and the loss of neuronal or synaptic SIRT1 [35]. To further assess the role of SIRT1, activity was measured and compared to control, with SIRT1 activity reduced in all disease groups although no significant difference was seen between disease groups.…”

Section: Discussionmentioning

confidence: 99%

SIRT1 ameliorates oxidative stress induced neural cell death and is down-regulated in Parkinson’s disease

2017

View full text Add to dashboard Cite

Background Sirtuins (SIRTs) are NAD+ dependent lysine deacetylases which are conserved from bacteria to humans and have been associated with longevity and lifespan extension. SIRT1, the best studied mammalian SIRT is involved in many physiological and pathological processes and changes in SIRT1 have been implicated in neurodegenerative disorders, with SIRT1 having a suggested protective role in Parkinson’s disease. In this study, we determined the effect of SIRT1 on cell survival and α-synuclein aggregate formation in SH-SY5Y cells following oxidative stress.ResultsOver-expression of SIRT1 protected SH-SY5Y cells from toxin induced cell death and the protection conferred by SIRT1 was partially independent of its deacetylase activity, which was associated with the repression of NF-кB and cPARP expression. SIRT1 reduced the formation of α-synuclein aggregates but showed minimal co-localisation with α-synuclein. In post-mortem brain tissue obtained from patients with Parkinson’s disease, Parkinson’s disease with dementia, dementia with Lewy bodies and Alzheimer’s disease, the activity of SIRT1 was observed to be down-regulated.ConclusionsThese findings suggests a negative effect of oxidative stress in neurodegenerative disorders and possibly explain the reduced activity of SIRT1 in neurodegenerative disorders. Our study shows that SIRT1 is a pro-survival protein that is downregulated under cellular stress.Electronic supplementary materialThe online version of this article (doi:10.1186/s12868-017-0364-1) contains supplementary material, which is available to authorized users.

show abstract

Section: Discussionmentioning

confidence: 99%

SIRT1 ameliorates oxidative stress induced neural cell death and is down-regulated in Parkinson’s disease

2017

View full text Add to dashboard Cite

show abstract

“…For example, important differences in the characteristics of plaques in human AD and APP/PS1 mice may provide different mechanisms of MR contrast changes: plaques in APP/PS1 mice contain less iron, but are more densely packed compared with human AD samples [53]. Using voxel-based quantification, Su et al found that AD was characterised by reduced T 1 values in certain brain regions, including bilateral temporal and parietal lobes in cross-sectional comparison, and an increase in T 1 in the right caudate, bilateral hippocampus, parahippocampus, and thalamus in longitudinal comparison [20]. Increased T 1 values in white matter of AD patients has been reported [54], and taken together this demonstrates the complex nature of T 1 changes in the human AD brain.…”

Section: Discussionmentioning

confidence: 99%

“…In a cross-sectional analysis of 21 subjects with AD and 32 similarly aged healthy controls, AD was characterised by reduced quantitative T 1 and T 2 values [20]. In previous work by the same authors, decreased T 1 values were found in patients with dementia with Lewy bodies compared with control subjects, highlighting the potential of T 1 measures in general to detect changes caused by neurodegeneration [21].…”

Section: Introductionmentioning

confidence: 99%

Can MRI T1 be used to detect early changes in 5xFAD Alzheimer’s mouse brain?

Spencer

Lovell

Elderfield

et al. 2016

Magn Reson Mater Phy

View full text Add to dashboard Cite

ObjectivesIn the present study, we have tested whether MRI T1 relaxation time is a sensitive marker to detect early stages of amyloidosis and gliosis in the young 5xFAD transgenic mouse, a well-established animal model for Alzheimer’s disease.Materials and methods5xFAD and wild-type mice were imaged in a 4.7 T Varian horizontal bore MRI system to generate T1 quantitative maps using the spin-echo multi-slice sequence. Following immunostaining for glial fibrillary acidic protein, Iba-1, and amyloid-β, T1 and area fraction of staining were quantified in the posterior parietal and primary somatosensory cortex and corpus callosum.ResultsIn comparison with age-matched wild-type mice, we observed first signs of amyloidosis in 2.5-month-old 5xFAD mice, and development of gliosis in 5-month-old 5xFAD mice. In contrast, MRI T1 relaxation times of young, i.e., 2.5- and 5-month-old, 5xFAD mice were not significantly different to those of age-matched wild-type controls. Furthermore, although disease progression was detectable by increased amyloid-β load in the brain of 5-month-old 5xFAD mice compared with 2.5-month-old 5xFAD mice, MRI T1 relaxation time did not change.ConclusionsIn summary, our data suggest that MRI T1 relaxation time is neither a sensitive measure of disease onset nor progression at early stages in the 5xFAD mouse transgenic mouse model.

show abstract

“…A primary limitation of postmortem studies is the inability to perform longitudinal assessment of regional brain atrophy in individual patients. Conventional MRI studies using cortical volumetric analysis have provided significant insight into longitudinal changes in regional atrophy associated with different subtypes of dementia [84][85][86]. We have shown that our in vivo technique with ultra-high field MRI can be used for similar studies of midbrain nuclei in PD.…”

Section: Future Directionsmentioning

confidence: 95%

Substantia Nigra Volume Dissociates Bradykinesia and Rigidity from Tremor in Parkinson’s Disease: A 7 Tesla Imaging Study

Poston

Cruadhlaoich

Santoso

et al. 2020

JPD

View full text Add to dashboard Cite

Background: In postmortem analysis of late stage Parkinson's disease (PD) neuronal loss in the substantial nigra (SN) correlates with the antemortem severity of bradykinesia and rigidity, but not tremor. Objective: To investigate the relationship between midbrain nuclei volume as an in vivo biomarker for surviving neurons in mild-to-moderate patients using 7.0 Tesla MRI. Methods: We performed ultra-high resolution quantitative susceptibility mapping (QSM) on the midbrain in 32 PD participants with less than 10 years duration and 8 healthy controls. Following blinded manual segmentation, the individual volumes of the SN, subthalamic nucleus, and red nucleus were measured. We then determined the associations between the midbrain nuclei and clinical metrics (age, disease duration, MDS-UPDRS motor score, and subscores for bradykinesia/rigidity, tremor, and postural instability/gait difficulty). Results: We found that smaller SN correlated with longer disease duration (r =-0.49, p = 0.004), more severe MDS-UPDRS motor score (r =-0.42, p = 0.016), and more severe bradykinesia-rigidity subscore (r =-0.47, p = 0.007), but not tremor or postural instability/gait difficulty subscores. In a hemi-body analysis, bradykinesia-rigidity severity only correlated with SN contralateral to the less-affected hemi-body, and not contralateral to the more-affected hemi-body, possibly reflecting the greatest change in dopamine neuron loss early in disease. Multivariate generalized estimating equation model confirmed that bradykinesia-rigidity severity, age, and disease duration, but not tremor severity, predicted SN volume. Conclusions: In mild-to-moderate PD, SN volume relates to motor manifestations in a motor domain-specific and lateralitydependent manner. Non-invasive in vivo 7.0 Tesla QSM may serve as a biomarker in longitudinal studies of SN atrophy and in studies of people at risk for developing PD.

show abstract

Cortical and Subcortical Changes in Alzheimer's Disease: A Longitudinal and Quantitative MRI Study

Cited by 21 publications

References 29 publications

SIRT1 ameliorates oxidative stress induced neural cell death and is down-regulated in Parkinson’s disease

SIRT1 ameliorates oxidative stress induced neural cell death and is down-regulated in Parkinson’s disease

Can MRI T1 be used to detect early changes in 5xFAD Alzheimer’s mouse brain?

Substantia Nigra Volume Dissociates Bradykinesia and Rigidity from Tremor in Parkinson’s Disease: A 7 Tesla Imaging Study

Contact Info

Product

Resources

About