scholarly journals Studies on Interaction of Buffalo Brain Cystatin with Donepezil: An Alzheimer's Drug

2013 ◽  
Vol 2013 ◽  
pp. 1-7 ◽  
Author(s):  
Fakhra Amin ◽  
Bilqees Bano
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Conformational Change ◽  
Structural Changes ◽  
Gel Filtration ◽  
Alkaline Treatment ◽  
Uv Spectra ◽  
Cysteine Protease Inhibitor ◽  
Native Page ◽  
Ammonium Sulphate Fractionation

When drugs bind to a protein, the intramolecular structures can be altered, resulting in conformational change of the protein. Donepezil, an Acetyl Cholinesterase inhibitor (AChE), is commonly prescribed to patients with Alzheimer's disease (AD) to enhance cholinergic neurotransmission. It is the “first-line” agents in the treatment of Alzheimer's disease used to improve cognitive function in the disease. In the present study, a cysteine protease inhibitor (cystatin) has been isolated from buffalo brain using alkaline treatment, 40 to 60% ammonium sulphate fractionation and gel filtration chromatography on Sephadex G-75 with % yield of 64.13 and fold purification of 384.7. The purified inhibitor (Buffalo Brain Cystatin, (BBC)) was eluted as a single papain inhibitory peak which migrated as single band on native PAGE; however, on SDS-PAGE with and without beta mercaptoethanol (βME) BBC gave two bands of M W 31.6 and 12.4 KDa, respectively. The molecular weight determined by gel filtration came out to be 43.6 KDa. The UV spectra of cystatin on interaction with donepezil suggested a conformational change in the protein. The fluorescence spectra of BC-donepezil composite show structural changes indicating 40 nm red shift with significant increase in fluorescence intensity of cystatin in the presence of donepezil representing an unfolding of cystatin on interaction, which is an indication of side effect of donepezil during the use of this drug.

scholarly journals Commonalities between Copper Neurotoxicity and Alzheimer’s Disease

Toxics ◽  
2021 ◽  
Vol 9 (1) ◽  
pp. 4
Author(s):  
Roshni Patel ◽  
Michael Aschner
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Structural Changes ◽  
Copper Ion ◽  
Plaque Formation ◽  
Ion Concentration ◽  
Medical Community ◽  
Disease Etiology ◽  
Parent Protein ◽  
Lead Zinc

Alzheimer’s disease, a highly prevalent form of dementia, targets neuron function beginning from the hippocampal region and expanding outwards. Alzheimer’s disease is caused by elevated levels of heavy metals, such as lead, zinc, and copper. Copper is found in many areas of daily life, raising a concern as to how this metal and Alzheimer’s disease are related. Previous studies have not identified the common pathways between excess copper and Alzheimer’s disease etiology. Our review corroborates that both copper and Alzheimer’s disease target the hippocampus, cerebral cortex, cerebellum, and brainstem, affecting motor skills and critical thinking. Additionally, Aβ plaque formation was analyzed beginning from synthesis at the APP parent protein site until Aβ plaque formation was completed. Structural changes were also noted. Further analysis revealed a relationship between amyloid-beta plaques and copper ion concentration. As copper ion levels increased, it bound to the Aβ monomer, expediting the plaque formation process, and furthering neurodegeneration. These conclusions can be utilized in the medical community to further research on the etiology of Alzheimer’s disease and its relationships to copper and other metal-induced neurotoxicity.

scholarly journals Changes in retinal microvasculature and retinal layer thickness in association with apolipoprotein E genotype in Alzheimer’s disease

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Joo Youn Shin ◽  
Eun Young Choi ◽  
Min Kim ◽  
Hyung Keun Lee ◽  
Suk Ho Byeon
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Layer Thickness ◽  
Structural Changes ◽  
Foveal Avascular Zone ◽  
Retinal Layer ◽  
Inner Plexiform Layer ◽  
Apoe Ε4 ◽  
Retinal Microvasculature ◽  
Capillary Plexus

AbstractBiomarker tests of Alzheimer’s disease (AD) are invasive and expensive. Recent developments in optical coherence tomography (OCT) and OCT angiography (OCTA) have enabled noninvasive, cost-effective characterization of retinal layer vasculature and thickness. Using OCTA and OCT, we characterized retinal microvascular changes in the mild cognitive impairment (MCI) stage of AD and assessed their correlation with structural changes in each retinal neuronal layer. We also evaluated the effect of the APOE-ε4 genotype on retinal microvasculature and layer thickness. Retinal layer thickness did not differ between MCI patients (40 eyes) and controls (37 eyes, all p > 0.05). MCI patients had lower vessel density (VD) (p = 0.003) of the superficial capillary plexus (SCP) and larger foveal avascular zone area (p = 0.01) of the deep capillary plexus (DCP) than those of controls. VD of the SCP correlated with the ganglion cell layer (r = 0.358, p = 0.03) and inner plexiform layer thickness (r = 0.437, p = 0.007) in MCI patients. APOE-ε4-carrying MCI patients had a lower VD of the DCP than non-carriers (p = 0.03). In conclusion, retinal microvasculature was reduced in patients with AD-associated MCI, but retinal thickness was not changed; these changes might be affected by the APOE genotype. OCTA of the retinal microvasculature may be useful to detect vascular changes in AD.

Structural Changes in Thalamic Nuclei Across Prodromal and Clinical Alzheimer’s Disease

2021 ◽  
pp. 1-11
Author(s):  
Adam S. Bernstein ◽  
Steven Z. Rapcsak ◽  
Michael Hornberger ◽  
Manojkumar Saranathan ◽  
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Large Scale ◽  
Structural Changes ◽  
Thalamic Nuclei ◽  
Medial Temporal Lobes ◽  
Cognitive Changes ◽  
Temporal Lobes ◽  
Medial Geniculate ◽  
Healthy Control

Background: Increasing evidence suggests that thalamic nuclei may atrophy in Alzheimer’s disease (AD). We hypothesized that there will be significant atrophy of limbic thalamic nuclei associated with declining memory and cognition across the AD continuum. Objective: The objective of this work was to characterize volume differences in thalamic nuclei in subjects with early and late mild cognitive impairment (MCI) as well as AD when compared to healthy control (HC) subjects using a novel MRI-based thalamic segmentation technique (THOMAS). Methods: MPRAGE data from the ADNI database were used in this study (n = 540). Healthy control (n = 125), early MCI (n = 212), late MCI (n = 114), and AD subjects (n = 89) were selected, and their MRI data were parcellated to determine the volumes of 11 thalamic nuclei for each subject. Volumes across the different clinical subgroups were compared using ANCOVA. Results: There were significant differences in thalamic nuclei volumes between HC, late MCI, and AD subjects. The anteroventral, mediodorsal, pulvinar, medial geniculate, and centromedian nuclei were significantly smaller in subjects with late MCI and AD when compared to HC subjects. Furthermore, the mediodorsal, pulvinar, and medial geniculate nuclei were significantly smaller in early MCI when compared to HC subjects. Conclusion: This work highlights nucleus specific atrophy within the thalamus in subjects with early and late MCI and AD. This is consistent with the hypothesis that memory and cognitive changes in AD are mediated by damage to a large-scale integrated neural network that extends beyond the medial temporal lobes.

scholarly journals Functional connectivity of the nucleus basalis of Meynert in Lewy body dementia and Alzheimer’s disease

2021 ◽  
pp. 1-6
Author(s):  
Julia Schumacher ◽  
Alan J. Thomas ◽  
Luis R. Peraza ◽  
Michael Firbank ◽  
John T. O’Brien ◽  
...  
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Functional Connectivity ◽  
Lewy Body ◽  
Cholinergic System ◽  
Structural Changes ◽  
Lewy Body Dementia ◽  
Occipital Cortex ◽  
Nucleus Basalis ◽  
Nucleus Basalis Of Meynert

ABSTRACT Cholinergic deficits are a hallmark of Alzheimer’s disease (AD) and Lewy body dementia (LBD). The nucleus basalis of Meynert (NBM) provides the major source of cortical cholinergic input; studying its functional connectivity might, therefore, provide a tool for probing the cholinergic system and its degeneration in neurodegenerative diseases. Forty-six LBD patients, 29 AD patients, and 31 healthy age-matched controls underwent resting-state functional magnetic resonance imaging (fMRI). A seed-based analysis was applied with seeds in the left and right NBM to assess functional connectivity between the NBM and the rest of the brain. We found a shift from anticorrelation in controls to positive correlations in LBD between the right/left NBM and clusters in right/left occipital cortex. Our results indicate that there is an imbalance in functional connectivity between the NBM and primary visual areas in LBD, which provides new insights into alterations within a part of the corticopetal cholinergic system that go beyond structural changes.

scholarly journals Retinal Functional and Structural Changes in the 5xFAD Mouse Model of Alzheimer’s Disease

2020 ◽  
Vol 14 ◽  
Author(s):  
Jeremiah K. H. Lim ◽  
Qiao-Xin Li ◽  
Zheng He ◽  
Algis J. Vingrys ◽  
Holly R. Chinnery ◽  
...  
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Mouse Model ◽  
Structural Changes ◽  
Model Of Alzheimer’S Disease ◽  
5Xfad Mouse

scholarly journals The association between biomarkers in cerebrospinal fluid and structural changes in the brain in patients with Alzheimer's disease

2013 ◽  
Vol 275 (4) ◽  
pp. 418-427 ◽  
Author(s):  
X. Li ◽  
T.-Q. Li ◽  
N. Andreasen ◽  
M. K. Wiberg ◽  
E. Westman ◽  
...  
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Cerebrospinal Fluid ◽  
Structural Changes ◽  
The Brain

scholarly journals E22Δ Mutation in Amyloidβ-Protein Promotesβ-Sheet Transformation, Radical Production, and Synaptotoxicity, But Not Neurotoxicity

2011 ◽  
Vol 2011 ◽  
pp. 1-8 ◽  
Author(s):  
Takayuki Suzuki ◽  
Kazuma Murakami ◽  
Naotaka Izuo ◽  
Toshiaki Kume ◽  
Akinori Akaike ◽  
...  
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Cognitive Decline ◽  
Conformational Change ◽  
Deletion Mutant ◽  
Protein A ◽  
Type A ◽  
Synaptic Dysfunction ◽  
Wild Type ◽  
Radical Production

Oligomers of 40- or 42-mer amyloidβ-protein (Aβ40, Aβ42) cause cognitive decline and synaptic dysfunction in Alzheimer's disease. We proposed the importance of a turn at Glu22 and Asp23 of Aβ42 to induce its neurotoxicity through the formation of radicals. Recently, a novel deletion mutant at Glu22 (E22Δ) of Aβ42 was reported to accelerate oligomerization and synaptotoxicity. To investigate this mechanism, the effects of the E22Δ mutation in Aβ42 and Aβ40 on the transformation ofβ-sheets, radical production, and neurotoxicity were examined. Both mutants promotedβ-sheet transformation and the formation of radicals, while their neurotoxicity was negative. In contrast, E22P-Aβ42 with a turn at Glu22 and Asp23 exhibited potent neurotoxicity along with the ability to form radicals and potent synaptotoxicity. These data suggest that conformational change in E22Δ-Aβis similar to that in E22P-Aβ42 but not the same, since E22Δ-Aβ42 exhibited no cytotoxicity, unlike E22P-Aβ42 and wild-type Aβ42.

scholarly journals Moderating Effect of Insulin Resistance on the Relationship between Gray Matter Volumes and Cognitive Function

2018 ◽  
Vol 7 (11) ◽  
pp. 413 ◽  
Author(s):  
Jiyeon Lee ◽  
Jihyeon Kim ◽  
Seong Shin ◽  
Soowon Park ◽  
Dong Yoon ◽  
...  
Keyword(s):  
Alzheimer’S Disease ◽  
Insulin Resistance ◽  
Alzheimer's Disease ◽  
Cognitive Function ◽  
Cognitive Decline ◽  
Gray Matter ◽  
Structural Changes ◽  
Gray Matter Volume ◽  
Volume Loss ◽  
Matter Volume

Background: It is controversial whether exposure to insulin resistance accelerates cognitive deterioration. The present study aimed to investigate the association between insulin resistance and gray matter volume loss to predict the cognitive decline. Methods: We recruited 160 participants (78 with Alzheimer’s disease and 82 without Alzheimer’s disease). Insulin resistance, regional gray matter volume, and cognitive function were assessed. A hierarchical moderated multiple regression (MMR) model was used to determine any associations among insulin resistance, structural changes in the brain, and cognitive decline. Results: The volumes of 7 regions in the gray matter were negatively related to insulin resistance in Alzheimer’s disease (p =0.032). Hierarchical MMR analysis indicated that insulin resistance did not directly affect the cognitive decline but moderated the cognitive decline through the decrease in gray matter volume in the key brain regions, i.e., inferior orbitofrontal gyrus (left), middle cingulate gyrus (right), hippocampus (right), and precuneus (right) (p < 0.05 in each case). Conclusion: Insulin resistance appears to exacerbate the cognitive decline associated with several gray matter volume loss.

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