PET/MRI Delivers Multimodal Brain Signature in Alzheimer’s Disease with De Novo PSEN1 Mutation

2021 ◽  
Vol 18 ◽  
Author(s):  
Gayane Aghakhanyan ◽  
Dorothee Saur ◽  
Michael Rullmann ◽  
Christopher M. Weise ◽  
Matthias L. Schroeter ◽  
...  
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
De Novo ◽  
Diffusion Tensor ◽  
Molecular Genetic ◽  
Pathogenic Variant ◽  
Stage Iii ◽  
Braak Stage ◽  
Subcortical Structures ◽  
Functional Brain

Background: Little is known so far about the brain phenotype and the spatial interplay of different Alzheimer’s disease (AD) biomarkers with structural and functional brain connectivity in the early phase of autosomal-dominant AD (ADAD). Multimodal PET/MRI might be suitable to fill this gap. Material and Methods: We presented a 31-year-old male patient without a family history of de- mentia with progressive worsening of memory and motor function. Two separate sessions of 3T PET/MRI acquisitions were arranged with the ß-amyloid tracer [18F]Florbetaben and the second-- generation tau tracer [18F]PI-2620. Simultaneously acquired MRI consisted of high-resolution 3D T1, diffusion-tensor imaging (DTI), and resting-state fMRI. PET/MRI data were compared with ten age-matched healthy controls. Results: Widespread β-amyloid depositions were found in cortical regions, and striatum (Thal stage III) along with tau pathology restricted to the mesial-temporal structures (Braak stage III/IV). Volumetric/shape analysis of subcortical structures revealed atrophy of the hippocampal-amygdala complex. In addition, cortical thinning was detected in the right middle temporal pole. Alterations of multiple DTI indices were noted in the major white matter fiber bundles, together with disrup- tion of default mode and sensory-motor network functional connectivity. Molecular genetic analy- sis by next-generation sequencing revealed a heterozygote missense pathogenic variant of the PSEN1 (Met233Val). Conclusion: Multimodal PET/MR imaging is able to deliver, in a one-stop-shop approach, an ar- ray of molecular, structural and functional brain information in AD due to de novo pathogenic variant, which can be studied for spatial interplay and might provide a rationale for initiating an- ti-amyloid/tau therapeutic approaches.

scholarly journals Upregulation of Local Hepcidin Contributes to Iron Accumulation in Alzheimer’s Disease Brains

2021 ◽  
pp. 1-11
Author(s):  
Suman Chaudhary ◽  
Ajay Ashok ◽  
Dallas McDonald ◽  
Aaron S. Wise ◽  
Alexander E. Kritikos ◽  
...  
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Amyloid Β ◽  
Stage I ◽  
Iron Accumulation ◽  
Stage Iii ◽  
Braak Stage ◽  
Tissue Iron ◽  
Consistent Feature ◽  
Total Tissue

Background: Accumulation of iron is a consistent feature of Alzheimer’s disease (AD) brains. The underlying cause, however, remains debatable. Objective: To explore whether local hepcidin synthesized by brain cells contributes to iron accumulation in AD brains. Methods: Brain tissue from the cingulate cortex of 33 cases of AD pre-assigned to Braak stage I-VI, 6 cases of non-dementia, and 15 cases of non-AD dementia were analyzed for transcriptional upregulation of hepcidin by RT-qPCR and RT-PCR. Change in the expression of ferritin, ferroportin (Fpn), microglial activation marker Iba1, IL-6, and TGFβ2 was determined by western blotting. Total tissue iron was determined by colorimetry. Results: Significant transcriptional upregulation of hepcidin was observed in Braak stage III-VI relative to Braak stage I and II, non-AD dementia, and non-dementia samples. Ferritin was increased in Braak stage V, and a significant increase in tissue iron was evident in Braak stage III-VI. The expression of Iba1 and IL-6 was also increased in Braak stage III-VI relative to Braak stage I and II and non-AD dementia samples. Amyloid-β plaques were absent in most Braak stage I and II samples, and present in Braak stage III-VI samples with few exceptions. Conclusion: These observations suggest that upregulation of brain hepcidin is mediated by IL-6, a known transcriptional activator of hepcidin. The consequent downregulation of Fpn on neuronal and other cells results in accumulation of iron in AD brains. The increase in hepcidin is disease-specific, and increases with disease progression, implicating AD-specific pathology in the accumulation of iron.

scholarly journals Machine Learning for the Classification of Alzheimer’s Disease and Its Prodromal Stage Using Brain Diffusion Tensor Imaging Data: A Systematic Review

Processes ◽  
2020 ◽  
Vol 8 (9) ◽  
pp. 1071
Author(s):  
Lucia Billeci ◽  
Asia Badolato ◽  
Lorenzo Bachi ◽  
Alessandro Tonacci
Keyword(s):  
Machine Learning ◽  
Systematic Review ◽  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Diffusion Tensor Imaging ◽  
Magnetic Resonance ◽  
Diffusion Tensor ◽  
Classification Problem ◽  
Computer Algorithms ◽  
Imaging Data

Alzheimer’s disease is notoriously the most common cause of dementia in the elderly, affecting an increasing number of people. Although widespread, its causes and progression modalities are complex and still not fully understood. Through neuroimaging techniques, such as diffusion Magnetic Resonance (MR), more sophisticated and specific studies of the disease can be performed, offering a valuable tool for both its diagnosis and early detection. However, processing large quantities of medical images is not an easy task, and researchers have turned their attention towards machine learning, a set of computer algorithms that automatically adapt their output towards the intended goal. In this paper, a systematic review of recent machine learning applications on diffusion tensor imaging studies of Alzheimer’s disease is presented, highlighting the fundamental aspects of each work and reporting their performance score. A few examined studies also include mild cognitive impairment in the classification problem, while others combine diffusion data with other sources, like structural magnetic resonance imaging (MRI) (multimodal analysis). The findings of the retrieved works suggest a promising role for machine learning in evaluating effective classification features, like fractional anisotropy, and in possibly performing on different image modalities with higher accuracy.

scholarly journals Mitochondrial complex I abnormalities is associated with tau and clinical symptoms in mild Alzheimer’s disease

2021 ◽  
Vol 16 (1) ◽  
Author(s):  
Tatsuhiro Terada ◽  
Joseph Therriault ◽  
Min Su Peter Kang ◽  
Melissa Savard ◽  
Tharick Ali Pascoal ◽  
...  
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Mitochondrial Dysfunction ◽  
Complex I ◽  
Clinical Symptoms ◽  
Mitochondrial Complex I ◽  
Braak Stage ◽  
Mitochondrial Complex ◽  
Temporal Area

Abstract Background Mitochondrial electron transport chain abnormalities have been reported in postmortem pathological specimens of Alzheimer’s disease (AD). However, it remains unclear how amyloid and tau are associated with mitochondrial dysfunction in vivo. The purpose of this study is to assess the local relationships between mitochondrial dysfunction and AD pathophysiology in mild AD using the novel mitochondrial complex I PET imaging agent [18F]BCPP-EF. Methods Thirty-two amyloid and tau positive mild stage AD dementia patients (mean age ± SD: 71.1 ± 8.3 years) underwent a series of PET measurements with [18F]BCPP-EF mitochondrial function, [11C]PBB3 for tau deposition, and [11C] PiB for amyloid deposition. Age-matched normal control subjects were also recruited. Inter and intrasubject comparisons of levels of mitochondrial complex I activity, amyloid and tau deposition were performed. Results The [18F]BCPP-EF uptake was significantly lower in the medial temporal area, highlighting the importance of the mitochondrial involvement in AD pathology. [11C]PBB3 uptake was greater in the temporo-parietal regions in AD. Region of interest analysis in the Braak stage I-II region showed significant negative correlation between [18F]BCPP-EF SUVR and [11C]PBB3 BPND (R = 0.2679, p = 0.04), but not [11C] PiB SUVR. Conclusions Our results indicated that mitochondrial complex I is closely associated with tau load evaluated by [11C]PBB3, which might suffer in the presence of its off-target binding. The absence of association between mitochondrial complex I dysfunction with amyloid load suggests that mitochondrial dysfunction in the trans-entorhinal and entorhinal region is a reflection of neuronal injury occurring in the brain of mild AD.

scholarly journals Joint Assessment of Structural, Perfusion, and Diffusion MRI in Alzheimer's Disease and Frontotemporal Dementia

2011 ◽  
Vol 2011 ◽  
pp. 1-11 ◽  
Author(s):  
Yu Zhang ◽  
Norbert Schuff ◽  
Christopher Ching ◽  
Duygu Tosun ◽  
Wang Zhan ◽  
...  
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Frontotemporal Dementia ◽  
Diffusion Tensor ◽  
Healthy Control ◽  
Multimodal Mri ◽  
Imaging Markers ◽  
And Diffusion ◽  
Joint Assessment ◽  
Diffusion Tensor Imaging Dti

Most MRI studies of Alzheimer's disease (AD) and frontotemporal dementia (FTD) have assessed structural, perfusion and diffusion abnormalities separately while ignoring the relationships across imaging modalities. This paper aimed to assess brain gray (GM) and white matter (WM) abnormalities jointly to elucidate differences in abnormal MRI patterns between the diseases. Twenty AD, 20 FTD patients, and 21 healthy control subjects were imaged using a 4 Tesla MRI. GM loss and GM hypoperfusion were measured using high-resolution T1 and arterial spin labeling MRI (ASL-MRI). WM degradation was measured with diffusion tensor imaging (DTI). Using a new analytical approach, the study found greater WM degenerations in FTD than AD at mild abnormality levels. Furthermore, the GM loss and WM degeneration exceeded the reduced perfusion in FTD whereas, in AD, structural and functional damages were similar. Joint assessments of multimodal MRI have potential value to provide new imaging markers for improved differential diagnoses between FTD and AD.

Aminotransferase Levels and Silymarin in de novo Tacrine-Treated Patients with Alzheimer’s Disease

1999 ◽  
Vol 10 (3) ◽  
pp. 181-185 ◽  
Author(s):  
H. Allain ◽  
S. Schück ◽  
S. Lebreton ◽  
A. Strenge-Hesse ◽  
W. Braun ◽  
...  
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
De Novo

Voxel-Based Diffusion Tensor Imaging of an APP/PS1 Mouse Model of Alzheimer’s Disease

2013 ◽  
Vol 48 (1) ◽  
pp. 78-83 ◽  
Author(s):  
Xiaogang Shu ◽  
Yuan-Yuan Qin ◽  
Shun Zhang ◽  
Jing-Jing Jiang ◽  
Yan Zhang ◽  
...  
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Diffusion Tensor Imaging ◽  
Mouse Model ◽  
Diffusion Tensor ◽  
Model Of Alzheimer’S Disease

FUNCTIONAL BRAIN ARCHITECTURE PREDICTS LONGITUDINAL TAU SPREADING IN ALZHEIMER’S DISEASE

2019 ◽  
Vol 15 (7) ◽  
pp. P1610-P1611
Author(s):  
Nicolai Franzmeier ◽  
Julia Neitzel ◽  
Anna Rubinski ◽  
Michael Ewers
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Functional Brain ◽  
Brain Architecture

Using Fractional Anisotropy Imaging to Detect Mild Cognitive Impairment and Alzheimer’s Disease among Mexican Americans and Non-Hispanic Whites: A HABLE Study

2021 ◽  
pp. 1-8
Author(s):  
James R. Hall ◽  
Leigh A. Johnson ◽  
Fan Zhang ◽  
Melissa Petersen ◽  
Arthur W. Toga ◽  
...  
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Cognitive Impairment ◽  
Mild Cognitive Impairment ◽  
Fractional Anisotropy ◽  
Mexican Americans ◽  
Diffusion Tensor ◽  
Characteristic Curve ◽  
Aging Brain ◽  
Community Based

<b><i>Introduction:</i></b> Alzheimer’s disease (AD) is the most frequently occurring neurodegenerative disease; however, little work has been conducted examining biomarkers of AD among Mexican Americans. Here, we examined diffusion tensor MRI marker profiles for detecting mild cognitive impairment (MCI) and dementia in a multi-ethnic cohort. <b><i>Methods:</i></b> 3T MRI measures of fractional anisotropy (FA) were examined among 1,636 participants of the ongoing community-based Health &amp; Aging Brain among Latino Elders (HABLE) community-based study (Mexican American <i>n</i> = 851; non-Hispanic white <i>n</i> = 785). <b><i>Results:</i></b> The FA profile was highly accurate in detecting both MCI (area under the receiver operating characteristic curve [AUC] = 0.99) and dementia (AUC = 0.98). However, the FA profile varied significantly not only between diagnostic groups but also between Mexican Americans and non-Hispanic whites. <b><i>Conclusion:</i></b> Findings suggest that diffusion tensor imaging markers may have a role in the neurodiagnostic process for detecting MCI and dementia among diverse populations.

Sign in / Sign up

Export Citation Format

Share Document