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.

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.

Fluoxetine Protects against Dendritic Spine Loss in Middle-aged APPswe/PSEN1dE9 Double Transgenic Alzheimer’s Disease Mice

2020 ◽  
Vol 17 (1) ◽  
pp. 93-103 ◽  
Author(s):  
Jing Ma ◽  
Yuan Gao ◽  
Wei Tang ◽  
Wei Huang ◽  
Yong Tang
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Dendritic Spines ◽  
Dendritic Spine ◽  
Early Stage ◽  
Learning Ability ◽  
Middle Aged ◽  
Protein Levels ◽  
Spine Pathology ◽  
The Impact

Background: Studies have suggested that cognitive impairment in Alzheimer’s disease (AD) is associated with dendritic spine loss, especially in the hippocampus. Fluoxetine (FLX) has been shown to improve cognition in the early stage of AD and to be associated with diminishing synapse degeneration in the hippocampus. However, little is known about whether FLX affects the pathogenesis of AD in the middle-tolate stage and whether its effects are correlated with the amelioration of hippocampal dendritic dysfunction. Previously, it has been observed that FLX improves the spatial learning ability of middleaged APP/PS1 mice. Objective: In the present study, we further characterized the impact of FLX on dendritic spines in the hippocampus of middle-aged APP/PS1 mice. Results: It has been found that the numbers of dendritic spines in dentate gyrus (DG), CA1 and CA2/3 of hippocampus were significantly increased by FLX. Meanwhile, FLX effectively attenuated hyperphosphorylation of tau at Ser396 and elevated protein levels of postsynaptic density 95 (PSD-95) and synapsin-1 (SYN-1) in the hippocampus. Conclusion: These results indicated that the enhanced learning ability observed in FLX-treated middle-aged APP/PS1 mice might be associated with remarkable mitigation of hippocampal dendritic spine pathology by FLX and suggested that FLX might be explored as a new strategy for therapy of AD in the middle-to-late stage.

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

P2-101: EVALUATION OF THE PRESYNAPTIC PROTEIN SNAP-25 AS A NOVEL CEREBROSPINAL FLUID MARKER FOR SYNAPTIC PATHOLOGY IN ALZHEIMER'S DISEASE

2014 ◽  
Vol 10 ◽  
pp. P508-P508
Author(s):  
Annika Öhrfelt ◽  
Gunnar Brinkmalm ◽  
William G. Honer ◽  
Lutz Frölich ◽  
Lucrezia Hausner ◽  
...  
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Cerebrospinal Fluid ◽  
Synaptic Pathology ◽  
Presynaptic Protein

TSPO and amyloid deposits in sub-regions of the hippocampus in the 3xTgAD mouse model of Alzheimer’s disease

2019 ◽  
Vol 121 ◽  
pp. 95-105 ◽  
Author(s):  
Benjamin B. Tournier ◽  
Stergios Tsartsalis ◽  
Daphney Rigaud ◽  
Christine Fossey ◽  
Thomas Cailly ◽  
...  
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Mouse Model ◽  
Model Of Alzheimer’S Disease ◽  
Amyloid Deposits

scholarly journals Morphology and Toxicity of Aβ-(1-42) Dimer Derived from Neuritic and Vascular Amyloid Deposits of Alzheimer's Disease

1996 ◽  
Vol 271 (34) ◽  
pp. 20631-20635 ◽  
Author(s):  
Alex E. Roher ◽  
Michael O. Chaney ◽  
Yu-Min Kuo ◽  
Scott D. Webster ◽  
W. Blaine Stine ◽  
...  
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Amyloid Deposits

scholarly journals Stabilization of dynamic microtubules by mDia1 drives Tau-dependent Aβ1–42 synaptotoxicity

2017 ◽  
Vol 216 (10) ◽  
pp. 3161-3178 ◽  
Author(s):  
Xiaoyi Qu ◽  
Feng Ning Yuan ◽  
Carlo Corona ◽  
Silvia Pasini ◽  
Maria Elena Pero ◽  
...  
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Axonal Transport ◽  
Dendritic Spines ◽  
Posttranslational Modifications ◽  
Hippocampal Neurons ◽  
Neuronal Damage ◽  
Driving Factors ◽  
Hyperphosphorylated Tau ◽  
Tau Hyperphosphorylation

Oligomeric Amyloid β1–42 (Aβ) plays a crucial synaptotoxic role in Alzheimer’s disease, and hyperphosphorylated tau facilitates Aβ toxicity. The link between Aβ and tau, however, remains controversial. In this study, we find that in hippocampal neurons, Aβ acutely induces tubulin posttranslational modifications (PTMs) and stabilizes dynamic microtubules (MTs) by reducing their catastrophe frequency. Silencing or acute inhibition of the formin mDia1 suppresses these activities and corrects the synaptotoxicity and deficits of axonal transport induced by Aβ. We explored the mechanism of rescue and found that stabilization of dynamic MTs promotes tau-dependent loss of dendritic spines and tau hyperphosphorylation. Collectively, these results uncover a novel role for mDia1 in Aβ-mediated synaptotoxicity and demonstrate that inhibition of MT dynamics and accumulation of PTMs are driving factors for the induction of tau-mediated neuronal damage.

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