scholarly journals Cortical and Subcortical Structural Segmentation in Alzheimer’s Disease

2019 ◽  
Author(s):  
Jafar Zamani ◽  
Ali Sadr ◽  
Amir-Homayoun Javadi
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Amyloid Beta ◽  
Clinical Symptoms ◽  
Brain Area ◽  
Brain Structures ◽  
Hippocampal Volume ◽  
Resonance Imaging ◽  
Brain Hemispheres ◽  
Subcortical Brain

Purpose: Alzheimer’s disease is a neurodegenerative disease that begins before clinical symptoms emerge. Amyloid-beta plaques and tau neurofibrillary tangles are the hallmark lesions of Alzheimer’s Disease (AD). Amyloid-beta plaques deposition is associated with increased hippocampal volume loss. The tissue volume measures reflect multiple underlying pathologies contributing to neurodegeneration, of which are the most characteristics of AD. Anatomical atrophy, as evidenced using Magnetic Resonance Imaging (MRI), is one of the most validated, easily accessible and widely used biomarkers of AD. Measurements of whole brain and hippocampal atrophy rates from serial structural MRI are potential markers of the underlying neuroaxonal damage and disease progression in AD. In this study, we extract automatically subcortical brain structures in AD and control subjects. Materials and Methods: In this study we used 20 images (10 AD patients and 10 controls) taken from the Minimal Interval Resonance Imaging in Alzheimer's Disease (MIRIAD) dataset. We obtained volumes of Cerebrospinal Fluid (CSF), White Matter (WM), Grey Matter (GM), brain hemispheres, cerebellum and brainstem using volBrain pipeline. Subcortical brain structure segments and related volumes and label maps information were extracted. We compared left and right sides of some of the important brain area in AD for obtaining a biomarker with brain atrophy. Amygdala, caudate and hippocampus have shown to be undergone atrophy in AD. Results: We provided volume information of some intracranial areas such as brain hemispheres, cerebellum and brainstem. Conclusion: The results showed smaller hippocampal volume in AD patients compared to the controls. In addition to hippocampus, similar atrophy is also observable in amygdala and caudate.

Is Olfactory Epithelium Biopsy Useful for Confirming Alzheimer’s Disease?

2018 ◽  
Vol 128 (3) ◽  
pp. 184-192 ◽  
Author(s):  
Maria Dantas Costa Lima Godoy ◽  
Marco Aurélio Fornazieri ◽  
Richard L. Doty ◽  
Fábio de Rezende Pinna ◽  
José Marcelo Farfel ◽  
...  
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Amyloid Beta ◽  
Olfactory Epithelium ◽  
Clinical Symptoms ◽  
Middle Turbinate ◽  
Superior Turbinate ◽  
Significant Difference ◽  
Amyloid Beta Proteins

Objectives: The clinical symptoms of Alzheimer’s disease (AD) are preceded by a long asymptomatic period associated with “silent” deposition of aberrant paired helical filament (PHF)-tau and amyloid-beta proteins in brain tissue. Similar depositions have been reported within the olfactory epithelium (OE), a tissue that can be biopsied in vivo. The degree to which such biopsies are useful in identifying AD is controversial. This postmortem study had 3 main goals: first, to quantify the relative densities of AD-related proteins in 3 regions of the olfactory neuroepithelium, namely, the nasal septum, middle turbinate, and superior turbinate; second, to establish whether such densities are correlated among these epithelial regions as well as with semi-quantitative ratings of general brain cortex pathology; and third, to evaluate correlations between the protein densities and measures of antemortem cognitive function. Methods: Postmortem blocks of olfactory mucosa were obtained from 12 AD cadavers and 24 controls and subjected to amyloid-beta and PHF-tau immunohistochemistry. Results: We observed marked heterogeneity in the presence of the biomarkers of tau and amyloid-beta among the targeted olfactory epithelial regions. No significant difference was observed between the cadavers with AD and the controls regarding the concentration of these proteins in any of these epithelial regions. Only one correlation significant was evident, namely, that between the tau protein densities of the middle and the upper turbinate ( r = .58, P = .002). Conclusion: AD-related biomarker heterogeneity, which has not been previously demonstrated, makes comparisons across studies difficult and throws into question the usefulness of OE amyloid-beta and PHF-tau biopsies in detecting AD.

scholarly journals Changes of Myelin Organization in Patients with Alzheimer’s Disease Shown by q-Space Myelin Map Imaging

2019 ◽  
Vol 9 (1) ◽  
pp. 24-33 ◽  
Author(s):  
Miho Ota ◽  
Noriko Sato ◽  
Yukio Kimura ◽  
Yoko Shigemoto ◽  
Hiroshi Kunugi ◽  
...  
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Healthy Subjects ◽  
Clinical Symptoms ◽  
Imaging Modality ◽  
Significant Negative Correlation ◽  
Anterior Cingulate ◽  
Resonance Imaging ◽  
Duration Of Illness ◽  
The Central Nervous System

Background: Recent studies detected the aberrant myelination of the central nervous system (CNS) in Alzheimer’s disease (AD). Here, we compared the change of myelination between patients with AD and controls by a novel magnetic resonance imaging modality, “q-space myelin map (MM) imaging.” Methods: Twenty patients with AD and 18 healthy subjects underwent MM imaging. We compared the MM metric between the 2 groups and examined the relationships between the metric and the clinical symptoms of AD. Results: AD patients showed a significant reduction of MM metric in the hippocampus, insula, precuneus, and anterior cingulate regions. There was also a significant negative correlation between the duration of illness and the MM metric in the temporoparietal region. Conclusion: Our findings suggest that MM imaging could be a clinically proper modality to estimate the myelination changes in AD patients.

scholarly journals Topological Dissection of Proteomic Changes Linked to the Limbic Stage of Alzheimer’s Disease

2021 ◽  
Vol 12 ◽  
Author(s):  
Erika Velásquez ◽  
Beáta Szeitz ◽  
Jeovanis Gil ◽  
Jimmy Rodriguez ◽  
Miklós Palkovits ◽  
...  
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Clinical Symptoms ◽  
Neurodegenerative Disorder ◽  
Brain Area ◽  
Disease Classification ◽  
Molecular Heterogeneity ◽  
Braak Stage ◽  
Tissue Samples ◽  
Major Player

Alzheimer’s disease (AD) is a neurodegenerative disorder and the most common cause of dementia worldwide. In AD, neurodegeneration spreads throughout different areas of the central nervous system (CNS) in a gradual and predictable pattern, causing progressive memory decline and cognitive impairment. Deposition of neurofibrillary tangles (NFTs) in specific CNS regions correlates with the severity of AD and constitutes the basis for disease classification into different Braak stages (I-VI). Early clinical symptoms are typically associated with stages III-IV (i.e., limbic stages) when the involvement of the hippocampus begins. Histopathological changes in AD have been linked to brain proteome alterations, including aberrant posttranslational modifications (PTMs) such as the hyperphosphorylation of Tau. Most proteomic studies to date have focused on AD progression across different stages of the disease, by targeting one specific brain area at a time. However, in AD vulnerable regions, stage-specific proteomic alterations, including changes in PTM status occur in parallel and remain poorly characterized. Here, we conducted proteomic, phosphoproteomic, and acetylomic analyses of human postmortem tissue samples from AD (Braak stage III-IV, n=11) and control brains (n=12), covering all anatomical areas affected during the limbic stage of the disease (total hippocampus, CA1, entorhinal and perirhinal cortices). Overall, ~6000 proteins, ~9000 unique phosphopeptides and 221 acetylated peptides were accurately quantified across all tissues. Our results reveal significant proteome changes in AD brains compared to controls. Among others, we have observed the dysregulation of pathways related to the adaptive and innate immune responses, including several altered antimicrobial peptides (AMPs). Notably, some of these changes were restricted to specific anatomical areas, while others altered according to disease progression across the regions studied. Our data highlights the molecular heterogeneity of AD and the relevance of neuroinflammation as a major player in AD pathology. Data are available via ProteomeXchange with identifier PXD027173.

scholarly journals Sex and APOE genotype influence Alzheimer’s disease tau neuropathology

2020 ◽  
Author(s):  
Paula Duarte-Guterman ◽  
Arianne Y. Albert ◽  
Cindy K. Barha ◽  
Liisa A.M. Galea
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Sex Differences ◽  
Cognitive Decline ◽  
Amyloid Beta ◽  
Brain Atrophy ◽  
Apoe Genotype ◽  
Hippocampal Volume ◽  
Amyloid Beta Protein ◽  
Biological Sex

ABSTRACTAlzheimer’s disease (AD) is characterised by severe cognitive decline and pathological changes in the brain (brain atrophy, hyperphosphorylation of tau, and deposition of toxic amyloid-beta protein). Females have worse neuropathology (AD biomarkers and brain atrophy rates) and cognitive decline than males, however biological sex can interact with diagnosis (mild cognitive impairment (MCI) or AD) and APOE genotype (number of ε4 alleles), although there are discrepancies between studies. Using the ADNI database, we analysed the effect of sex and APOE genotype (number of ε4 alleles) and sex and diagnosis (cognitively normal (CN), MCI, AD) on cognition (memory and executive function), hippocampal volume, CSF amyloid beta, CSF tau and ptau. More males were diagnosed with MCI but there was no sex difference in those diagnosed with AD, suggesting the progression from CN, MCI to AD may be sex-specific. We found, consistent with some studies, that females had higher levels of CSF tau-pathology that was disproportionately affected by APOE genotype compared to males. These results suggest that sex and APOE genotype effects on AD biomarkers may influence sex differences in incidence and progression of MCI and AD. We also detected sex differences in hippocampal volume but the direction was dependent on the method of correction. Females had better memory (including verbal) scores than males, which may suggest a delay in the onset of cognitive decline or diagnosis.

scholarly journals Sex-Dependent Age Trajectories of Subcortical Brain Structures: Analysis of Large-Scale Percentile Models and Shape Morphometry

2020 ◽  
Author(s):  
Christopher R. K. Ching ◽  
Zvart Abaryan ◽  
Vigneshwaran Santhalingam ◽  
Alyssa H. Zhu ◽  
Joanna K. Bright ◽  
...  
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Spatial Distribution ◽  
Large Scale ◽  
Brain Aging ◽  
Brain Structures ◽  
Large Sample Size ◽  
Subcortical Brain ◽  
Subcortical Brain Structures ◽  
Subcortical Volumes

ABSTRACTModeling of structural brain variation over the lifespan is important to better understand factors contributing to healthy aging and risk for neurological conditions such as Alzheimer’s disease. Even so, we lack normative data on brain morphometry across the adult lifespan in large, well-powered samples. Here, in a large population-based sample of 26,440 adults from the UK Biobank (age: 44-81 yrs.), we created normative percentile charts for MRI-derived subcortical volumes. Next, we investigated associations between these morphometric measures and the strongest known genetic risk factor for late-onset Alzheimer’s disease (APOE genotype) and mapped the spatial distribution of age-by-sex interactions using computational surface mesh modeling and shape analysis. Vertex-wise shape mapping supplements traditional gross volumetric approaches to reveal finer-grained variations across functionally important brain subcompartments. Normative curves revealed volumetric loss with age, as expected, for all subcortical brain structures except for the lateral ventricles, which expanded with age. Surprisingly, no volumetric associations with APOE genotype were detected, despite the very large sample size. Age-related trajectories for volumes differed in women versus men, and surface-based statistical maps revealed the spatial distribution of the age-by-sex interaction. Subcortical volumes declined faster in men than women over the full age range, but after age 60, fewer structures showed sex-dependent trajectories, indicating similar volumetric changes in older men and women. Large-scale statistical modeling of age effects on brain structures may drive new insights into individual differences in brain aging and help to identify factors that promote healthy brain aging and risk for disease.

Sign in / Sign up

Export Citation Format

Share Document