scholarly journals Analyzing Brain Morphology in Alzheimer's Disease Using Discriminative and Generative Spiral Networks

2021 ◽  
Author(s):  
Emanuel A. Azcona ◽  
Pierre Besson ◽  
Yunan Wu ◽  
Ajay S. Kurani ◽  
S. Kathleen Bandt ◽  
...  

Several patterns of atrophy have been identified and strongly related to Alzheimer's disease (AD) pathology and its progression. Morphological changes in brain shape have been identified up to ten years before clinical diagnoses of AD, making its early diagnosis more desirable. We propose novel geometric deep learning frameworks for the analysis of brain shape in the context of neurodegeneration caused by AD. Our deep neural networks learn low-dimensional shape descriptors of multiple neuroanatomical structures, instead of handcrafted features for each structure. A discriminative network using spiral convolution on 3D meshes is constructed for the in-vivo binary classification of AD from healthy controls (HCs) using a fast and efficient "spiral" convolution operator on 3D triangular mesh surfaces of human brain subcortical structures extracted from T1-weighted magnetic resonance imaging (MRI). Our network architecture consists of modular learning blocks using residual connections to improve overall classifier performance. In this work: (1) a discriminative network is used to analyze the efficacy of disease classification using input data from multiple brain structures and compared to using a single hemisphere or a single structure. It also outperforms prior work using spectral graph convolution on the same the same tasks, as well as alternative methods that operate on intermediate point cloud representations of 3D shapes. (2) Additionally, visual interpretations for regions on the surface of brain structures that are associated to true positive AD predictions are generated and fall in accordance with the current reports on the structural localization of pathological changes associated to AD. (3) A conditional generative network is also implemented to analyze the effects of phenotypic priors given to the model (i.e. AD diagnosis) in generating subcortical structures. The generated surface meshes by our model indicate learned morphological differences in the presence of AD that agrees with the current literature on patterns of atrophy associated to the disease. In particular, our inference results demonstrate an overall reduction in subcortical mesh volume and surface area in the presence of AD, especially in the hippocampus. The low-dimensional shape descriptors obtained by our generative model are also evaluated in our discriminative baseline comparisons versus our discriminative network and the alternative shape-based approaches.

2019 ◽  
Vol 20 (23) ◽  
pp. 5912
Author(s):  
Shaoxun Yuan ◽  
Haitao Li ◽  
Jianming Xie ◽  
Xiao Sun

The pathological features of Alzheimer’s Disease (AD) first appear in the medial temporal lobe and then in other brain structures with the development of the disease. In this work, we investigated the association between genetic loci and subcortical structure volumes of AD on 393 samples in the Alzheimer’s Disease Neuroimaging Initiative (ADNI) cohort. Brain subcortical structures were clustered into modules using Pearson’s correlation coefficient of volumes across all samples. Module volumes were used as quantitative traits to identify not only the main effect loci but also the interactive effect loci for each module. Thirty-five subcortical structures were clustered into five modules, each corresponding to a particular brain structure/area, including the limbic system (module I), the corpus callosum (module II), thalamus–cerebellum–brainstem–pallidum (module III), the basal ganglia neostriatum (module IV), and the ventricular system (module V). Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment results indicate that the gene annotations of the five modules were distinct, with few overlaps between different modules. We identified several main effect loci and interactive effect loci for each module. All these loci are related to the function of module structures and basic biological processes such as material transport and signal transduction.


2021 ◽  
Vol 22 (11) ◽  
pp. 6071
Author(s):  
Suzanne Gascon ◽  
Jessica Jann ◽  
Chloé Langlois-Blais ◽  
Mélanie Plourde ◽  
Christine Lavoie ◽  
...  

Alzheimer’s disease (AD) is a devastating neurodegenerative disease characterized by progressive neuron losses in memory-related brain structures. The classical features of AD are a dysregulation of the cholinergic system, the accumulation of amyloid plaques, and neurofibrillary tangles. Unfortunately, current treatments are unable to cure or even delay the progression of the disease. Therefore, new therapeutic strategies have emerged, such as the exogenous administration of neurotrophic factors (e.g., NGF and BDNF) that are deficient or dysregulated in AD. However, their low capacity to cross the blood–brain barrier and their exorbitant cost currently limit their use. To overcome these limitations, short peptides mimicking the binding receptor sites of these growth factors have been developed. Such peptides can target selective signaling pathways involved in neuron survival, differentiation, and/or maintenance. This review focuses on growth factors and their derived peptides as potential treatment for AD. It describes (1) the physiological functions of growth factors in the brain, their neuronal signaling pathways, and alteration in AD; (2) the strategies to develop peptides derived from growth factor and their capacity to mimic the role of native proteins; and (3) new advancements and potential in using these molecules as therapeutic treatments for AD, as well as their limitations.


Biomedicines ◽  
2021 ◽  
Vol 9 (7) ◽  
pp. 823
Author(s):  
Ekaterina A. Rudnitskaya ◽  
Tatiana A. Kozlova ◽  
Alena O. Burnyasheva ◽  
Natalia A. Stefanova ◽  
Nataliya G. Kolosova

Sporadic Alzheimer’s disease (AD) is a severe disorder of unknown etiology with no definite time frame of onset. Recent studies suggest that middle age is a critical period for the relevant pathological processes of AD. Nonetheless, sufficient data have accumulated supporting the hypothesis of “neurodevelopmental origin of neurodegenerative disorders”: prerequisites for neurodegeneration may occur during early brain development. Therefore, we investigated the development of the most AD-affected brain structures (hippocampus and prefrontal cortex) using an immunohistochemical approach in senescence-accelerated OXYS rats, which are considered a suitable model of the most common—sporadic—type of AD. We noticed an additional peak of neurogenesis, which coincides in time with the peak of apoptosis in the hippocampus of OXYS rats on postnatal day three. Besides, we showed signs of delayed migration of neurons to the prefrontal cortex as well as disturbances in astrocytic and microglial support of the hippocampus and prefrontal cortex during the first postnatal week. Altogether, our results point to dysmaturation during early development of the brain—especially insufficient glial support—as a possible “first hit” leading to neurodegenerative processes and AD pathology manifestation later in life.


2021 ◽  
Vol 10 (8) ◽  
pp. 1555
Author(s):  
Ágoston Patthy ◽  
János Murai ◽  
János Hanics ◽  
Anna Pintér ◽  
Péter Zahola ◽  
...  

Alzheimer’s disease (AD) is a devastating neurodegenerative disorder as yet without effective therapy. Symptoms of this disorder typically reflect cortical malfunction with local neurohistopathology, which biased investigators to search for focal triggers and molecular mechanisms. Cortex, however, receives massive afferents from caudal brain structures, which do not only convey specific information but powerfully tune ensemble activity. Moreover, there is evidence that the start of AD is subcortical. The brainstem harbors monoamine systems, which establish a dense innervation in both allo- and neocortex. Monoaminergic synapses can co-release neuropeptides either by precisely terminating on cortical neurons or, when being “en passant”, can instigate local volume transmission. Especially due to its early damage, malfunction of the ascending monoaminergic system emerges as an early sign and possible trigger of AD. This review summarizes the involvement and cascaded impairment of brainstem monoaminergic neurons in AD and discusses cellular mechanisms that lead to their dysfunction. We highlight the significance and therapeutic challenges of transmitter co-release in ascending activating system, describe the role and changes of local connections and distant afferents of brainstem nuclei in AD, and summon the rapidly increasing diagnostic window during the last few years.


2021 ◽  
Vol 18 ◽  
Author(s):  
Yuanyuan Wei ◽  
Nianwei Huang ◽  
Yong Liu ◽  
Xi Zhang ◽  
Silun Wang ◽  
...  

Background: Early detection of Alzheimer’s disease (AD) and its early stage, the mild cognitive impairment (MCI), has important scientific, clinical and social significance. Magnetic resonance imaging (MRI) based statistical shape analysis provides an opportunity to detect regional structural abnormalities of brain structures caused by AD and MCI. Objective: In this work, we aimed to employ a well-established statistical shape analysis pipeline, in the framework of large deformation diffeomorphic metric mapping, to identify and quantify the regional shape abnormalities of the bilateral hippocampus and amygdala at different prodromal stages of AD, using three Chinese MRI datasets collected from different domestic hospitals. Methods: We analyzed the region-specific shape abnormalities at different stages of the neuropathology of AD by comparing the localized shape characteristics of the bilateral hippocampi and amygdalas between healthy controls and two disease groups (MCI and AD). In addition to group comparison analyses, we also investigated the association between the shape characteristics and the Mini Mental State Examination (MMSE) of each structure of interest in the disease group (MCI and AD combined) as well as the discriminative power of different morphometric biomarkers. Results: We found the strongest disease pathology (regional atrophy) at the subiculum and CA1 subregions of the hippocampus and the basolateral, basomedial as well as centromedial subregions of the amygdala. Furthermore, the shape characteristics of the hippocampal and amygdalar subregions exhibiting the strongest AD related atrophy were found to have the most significant positive associations with the MMSE. Employing the shape deformation marker of the hippocampus or the amygdala for automated MCI or AD detection yielded a significant accuracy boost over the corresponding volume measurement. Conclusion: Our results suggested that the amygdalar and hippocampal morphometrics, especially those of shape morphometrics, can be used as auxiliary indicators for monitoring the disease status of an AD patient.


2021 ◽  
pp. 153537022110568
Author(s):  
Natalia V Bobkova ◽  
Daria Y Zhdanova ◽  
Natalia V Belosludtseva ◽  
Nikita V Penkov ◽  
Galina D Mironova

Here, we found that functionally active mitochondria isolated from the brain of NMRI donor mice and administrated intranasally to recipient mice penetrated the brain structures in a dose-dependent manner. The injected mitochondria labeled with the MitoTracker Red localized in different brain regions, including the neocortex and hippocampus, which are responsible for memory and affected by degeneration in patients with Alzheimer's disease. In behavioral experiments, intranasal microinjections of brain mitochondria of native NMRI mice improved spatial memory in the olfactory bulbectomized (OBX) mice with Alzheimer’s type degeneration. Control OBX mice demonstrated loss of spatial memory tested in the Morris water maze. Immunocytochemical analysis revealed that allogeneic mitochondria colocalized with the markers of astrocytes and neurons in hippocampal cell culture. The results suggest that a non-invasive route intranasal administration of mitochondria may be a promising approach to the treatment of neurodegenerative diseases characterized, like Alzheimer's disease, by mitochondrial dysfunction.


2006 ◽  
Vol 14 (7S_Part_16) ◽  
pp. P882-P883
Author(s):  
Erika Molteni ◽  
Thomas Veale ◽  
Andre Altmann ◽  
M. Jorge Cardoso ◽  
Tammie L.S. Benzinger ◽  
...  

2013 ◽  
Vol 9 ◽  
pp. P599-P599
Author(s):  
Hanna Cho ◽  
Jeong-Hun Kim ◽  
Byoung Seok Ye ◽  
Geon Ha Kim ◽  
Young Noh ◽  
...  

2021 ◽  
Author(s):  
Pierrick Coupé ◽  
José V. Manjón ◽  
Boris Mansencal ◽  
Thomas Tourdias ◽  
Gwenaëlle Catheline ◽  
...  

AbstractIn this paper, we present an innovative MRI-based method for Alzheimer’s Disease (AD) detection and mild cognitive impairment (MCI) prognostic, using lifespan trajectories of brain structures. After a full screening of the most discriminant structures between AD and normal aging based on MRI volumetric analysis of 3032 subjects, we propose a novel Hippocampal-Amygdalo-Ventricular Alzheimer score (HAVAs) based on normative lifespan models and AD lifespan models. During a validation on three external datasets on 1039 subjects, our approach showed very accurate detection (AUC ≥ 94%) of patients with AD compared to control subjects and accurate discrimination (AUC=78%) between progressive MCI and stable MCI (during a 3 years follow-up). Compared to normative modelling and recent state-of-the-art deep learning methods, our method demonstrated better classification performance. Moreover, HAVAs simplicity makes it fully understandable and thus well-suited for clinical practice or future pharmaceutical trials.


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