scholarly journals Mitochondria in the Cerebral and Cerebellar Cortex in Alzheimer’s Disease, Target for a Therapeutic Approach

2021 ◽  
Author(s):  
Stavros J. Baloyannis
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Cerebellar Cortex ◽  
Neurodegenerative Disorders ◽  
Energy Deficiency ◽  
Mitochondrial Alterations ◽  
Amyloid Deposits ◽  
Alzheimer’S Pathology ◽  
Normal Controls ◽  
Shape And Size

Alzheimer’s disease remains the main cause of dementia in advanced age worldwide. Among the etiopathological background of the disease mitochondrial alterations may play a crucial role, given that they are closely related to metabolic and energy deficiency in neurons, glia, and endothelial cells in Alzheimer’s disease and other neurodegenerative disorders. In a series of morphological and morphometric studies of mitochondria in the cerebrum and the cerebellar cortex in Alzheimer’s disease, by electron microscopy, we described marked morphological and morphometric alterations. The most frequent ultrastructural alterations of the mitochondria consist of disruption of the cristae, accumulation of osmiophilic material, and marked changes of shape and size in comparison with the normal controls. Mitochondrial alterations were particularly prominent in dendritic profiles and dendritic spines. The ultrastructural study of a substantial number of neurons in the cerebellum revealed that mitochondrial alterations do not coexist, as a rule, with the typical Alzheimer’s pathology, such as cytoskeletal alterations, amyloid deposits, and tau pathology, though they are frequently observed coexisting with alterations of the cisternae of the Golgi apparatus. Therapeutical regimes targeting mitochondria may be beneficial in early cases of Alzheimer’s disease.

scholarly journals Mitochondria Are Related to Synaptic Pathology in Alzheimer's Disease

2011 ◽  
Vol 2011 ◽  
pp. 1-7 ◽  
Author(s):  
Stavros J. Baloyannis
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Dendritic Spines ◽  
Red Nucleus ◽  
Morphological Alterations ◽  
Mitochondrial Alterations ◽  
Amyloid Deposits ◽  
Synaptic Pathology ◽  
Autopsy Specimens ◽  
Dendritic Branches

Morphological alterations of mitochondria may play an important role in the pathogenesis of Alzheimer's disease, been associated with oxidative stress and Aβ-peptide-induced toxicity. We proceeded to estimation of mitochondria on electron micrographs of autopsy specimens of Alzheimer's disease. We found substantial morphological and morphometric changes of the mitochondria in the neurons of the hippocampus, the neocortex, the cerebellar cortex, the thalamus, the globus pallidus, the red nucleus, the locus coeruleus, and the climbing fibers. The alterations consisted of considerable changes of the cristae, accumulation of osmiophilic material, and modification of the shape and size. Mitochondrial alterations were prominent in neurons, which showed a depletion of dendritic spines and loss of dendritic branches. Mitochondrial alterations are not related with the accumulation of amyloid deposits, but are prominent whenever fragmentation of the Golgi apparatus exists. Morphometric analysis showed also that mitochondria are significantly reduced in neurons, which demonstrated synaptic pathology.

Subjective Spatial Navigation Complaints - A Frequent Symptom Reported by Patients with Subjective Cognitive Decline, Mild Cognitive Impairment and Alzheimer's Disease

2018 ◽  
Vol 15 (3) ◽  
pp. 219-228 ◽  
Author(s):  
Jiri Cerman ◽  
Ross Andel ◽  
Jan Laczo ◽  
Martin Vyhnalek ◽  
Zuzana Nedelska ◽  
...  
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Cognitive Impairment ◽  
Mild Cognitive Impairment ◽  
Cognitive Decline ◽  
Spatial Navigation ◽  
Subjective Cognitive Decline ◽  
Great Effort ◽  
Frequent Symptom ◽  
Normal Controls

Background: Great effort has been put into developing simple and feasible tools capable to detect Alzheimer's disease (AD) in its early clinical stage. Spatial navigation impairment occurs very early in AD and is detectable even in the stage of mild cognitive impairment (MCI). Objective: The aim was to describe the frequency of self-reported spatial navigation complaints in patients with subjective cognitive decline (SCD), amnestic and non-amnestic MCI (aMCI, naMCI) and AD dementia and to assess whether a simple questionnaire based on these complaints may be used to detect early AD. Method: In total 184 subjects: patients with aMCI (n=61), naMCI (n=27), SCD (n=63), dementia due to AD (n=20) and normal controls (n=13) were recruited. The subjects underwent neuropsychological examination and were administered a questionnaire addressing spatial navigation complaints. Responses to the 15 items questionnaire were scaled into four categories (no, minor, moderate and major complaints). Results: 55% of patients with aMCI, 64% with naMCI, 68% with SCD and 72% with AD complained about their spatial navigation. 38-61% of these complaints were moderate or major. Only 33% normal controls expressed complaints and none was ranked as moderate or major. The SCD, aMCI and AD dementia patients were more likely to express complaints than normal controls (p's<0.050) after adjusting for age, education, sex, depressive symptoms (OR for SCD=4.00, aMCI=3.90, AD dementia=7.02) or anxiety (OR for SCD=3.59, aMCI=3.64, AD dementia=6.41). Conclusion: Spatial navigation complaints are a frequent symptom not only in AD, but also in SCD and aMCI and can potentially be detected by a simple and inexpensive questionnaire.

Allocentric to Egocentric Spatial Switching: Impairment in aMCI and Alzheimer's Disease Patients?

2018 ◽  
Vol 15 (3) ◽  
pp. 229-236 ◽  
Author(s):  
Gennaro Ruggiero ◽  
Alessandro Iavarone ◽  
Tina Iachini
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Reference Frame ◽  
Reference Frames ◽  
Memory Task ◽  
Spatial Representations ◽  
The Novel ◽  
Spatial Memory Task ◽  
Switching Condition ◽  
Normal Controls

Objective: Deficits in egocentric (subject-to-object) and allocentric (object-to-object) spatial representations, with a mainly allocentric impairment, characterize the first stages of the Alzheimer's disease (AD). Methods: To identify early cognitive signs of AD conversion, some studies focused on amnestic-Mild Cognitive Impairment (aMCI) by reporting alterations in both reference frames, especially the allocentric ones. However, spatial environments in which we move need the cooperation of both reference frames. Such cooperating processes imply that we constantly switch from allocentric to egocentric frames and vice versa. This raises the question of whether alterations of switching abilities might also characterize an early cognitive marker of AD, potentially suitable to detect the conversion from aMCI to dementia. Here, we compared AD and aMCI patients with Normal Controls (NC) on the Ego-Allo- Switching spatial memory task. The task assessed the capacity to use switching (Ego-Allo, Allo-Ego) and non-switching (Ego-Ego, Allo-Allo) verbal judgments about relative distances between memorized stimuli. Results: The novel finding of this study is the neat impairment shown by aMCI and AD in switching from allocentric to egocentric reference frames. Interestingly, in aMCI when the first reference frame was egocentric, the allocentric deficit appeared attenuated. Conclusion: This led us to conclude that allocentric deficits are not always clinically detectable in aMCI since the impairments could be masked when the first reference frame was body-centred. Alongside, AD and aMCI also revealed allocentric deficits in the non-switching condition. These findings suggest that switching alterations would emerge from impairments in hippocampal and posteromedial areas and from concurrent dysregulations in the locus coeruleus-noradrenaline system or pre-frontal cortex.

scholarly journals Two human metabolites rescue a C. elegans model of Alzheimer’s disease via a cytosolic unfolded protein response

2021 ◽  
Vol 4 (1) ◽  
Author(s):  
Priyanka Joshi ◽  
Michele Perni ◽  
Ryan Limbocker ◽  
Benedetta Mannini ◽  
Sam Casford ◽  
...  
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Unfolded Protein Response ◽  
Neurodegenerative Disorders ◽  
C Elegans ◽  
Unfolded Protein ◽  
Model Of Alzheimer’S Disease ◽  
Age Related ◽  
Parkinson’S Diseases ◽  
Protein Response

AbstractAge-related changes in cellular metabolism can affect brain homeostasis, creating conditions that are permissive to the onset and progression of neurodegenerative disorders such as Alzheimer’s and Parkinson’s diseases. Although the roles of metabolites have been extensively studied with regard to cellular signaling pathways, their effects on protein aggregation remain relatively unexplored. By computationally analysing the Human Metabolome Database, we identified two endogenous metabolites, carnosine and kynurenic acid, that inhibit the aggregation of the amyloid beta peptide (Aβ) and rescue a C. elegans model of Alzheimer’s disease. We found that these metabolites act by triggering a cytosolic unfolded protein response through the transcription factor HSF-1 and downstream chaperones HSP40/J-proteins DNJ-12 and DNJ-19. These results help rationalise previous observations regarding the possible anti-ageing benefits of these metabolites by providing a mechanism for their action. Taken together, our findings provide a link between metabolite homeostasis and protein homeostasis, which could inspire preventative interventions against neurodegenerative disorders.

scholarly journals Deep Learning with Neuroimaging and Genomics in Alzheimer’s Disease

2021 ◽  
Vol 22 (15) ◽  
pp. 7911
Author(s):  
Eugene Lin ◽  
Chieh-Hsin Lin ◽  
Hsien-Yuan Lane
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Deep Learning ◽  
Future Research ◽  
Learning Approaches ◽  
Learning Models ◽  
Learning Techniques ◽  
Neuroimaging Data ◽  
Similarities And Differences ◽  
Normal Controls

A growing body of evidence currently proposes that deep learning approaches can serve as an essential cornerstone for the diagnosis and prediction of Alzheimer’s disease (AD). In light of the latest advancements in neuroimaging and genomics, numerous deep learning models are being exploited to distinguish AD from normal controls and/or to distinguish AD from mild cognitive impairment in recent research studies. In this review, we focus on the latest developments for AD prediction using deep learning techniques in cooperation with the principles of neuroimaging and genomics. First, we narrate various investigations that make use of deep learning algorithms to establish AD prediction using genomics or neuroimaging data. Particularly, we delineate relevant integrative neuroimaging genomics investigations that leverage deep learning methods to forecast AD on the basis of incorporating both neuroimaging and genomics data. Moreover, we outline the limitations as regards to the recent AD investigations of deep learning with neuroimaging and genomics. Finally, we depict a discussion of challenges and directions for future research. The main novelty of this work is that we summarize the major points of these investigations and scrutinize the similarities and differences among these investigations.

Spectrum of morphological appearance of amyloid deposits in Alzheimer's disease

1989 ◽  
Vol 78 (4) ◽  
pp. 337-347 ◽  
Author(s):  
H. M. Wisniewski ◽  
C. Bancher ◽  
M. Barcikowska ◽  
G. Y. Wen ◽  
J. Currie
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Morphological Appearance ◽  
Amyloid Deposits
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