Amorphous hydroxyaluminium silicates formed under physiological saline conditions, and in CaCo3-buffered solutions. Stability and significance for Alzheimer plaque precipitates

AbstractIn an attempt to determine the nature and conditions of formation of the aluminium silicate precipitates present at the core of senile plaque in the brains of patients with Alzheimer's disease, aluminosilicate precipitates have been prepared and equilibrated for up to one year in physiological saline conditions at 40°C and a pH near 7·4. The structure and composition of these precipitates, and the associated concentrations of free silicic acid, were similar to those found in systems buffered with CaCO3at 20–25°C. Imogolite-like products with Si : Al ratios near 0·5 were obtained at silicic acid concentrations <100µm, and hydrous feldspathoid products with ratios ≥1·0 became dominant at silicic acid concentrations greater than ∼150µm. These products do not match senile plaque precipitates, which have Si : Al ratios ≥1·0, but form in an environment with <100µmSi. The relative stability of aluminium hydroxides, proto-imogolite allophane and hydrous feldspathoids are estimated from equilibrated silicic acid concentrations.

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Characteristics of Insulin-degrading Enzyme in Alzheimer's Disease: A Meta-Analysis

Current Alzheimer Research ◽

10.2174/1567205015666180119105446 ◽

2018 ◽

Vol 15 (7) ◽

pp. 610-617 ◽

Cited By ~ 4

Author(s):

Huifeng Zhang ◽

Dan Liu ◽

Huanhuan Huang ◽

Yujia Zhao ◽

Hui Zhou

Keyword(s):

Alzheimer’S Disease ◽

Alzheimer's Disease ◽

Enzyme Activity ◽

Protein Level ◽

Senile Plaque ◽

Meta Analysis ◽

Cochrane Library ◽

Insulin Degrading Enzyme ◽

Degrading Enzyme ◽

Significant Difference

Background: β-amyloid (Aβ) accumulates abnormally to senile plaque which is the initiator of Alzheimer's disease (AD). As one of the Aβ-degrading enzymes, Insulin-degrading enzyme (IDE) remains controversial for its protein level and activity in Alzheimer's brain. Methods: The electronic databases PubMed, EMBASE, The Cochrane Library, OVID and Sinomed were systemically searched up to Sep. 20th, 2017. And the published case-control or cohort studies were retrieved to perform the meta-analysis. Results: Seven studies for IDE protein level (AD cases = 293; controls = 126), three for mRNA level (AD cases = 138; controls = 81), and three for enzyme activity (AD cases = 123; controls = 75) were pooling together. The IDE protein level was significantly lower in AD cases than in controls (SMD = - 0.47, 95% CI [-0.69, -0.24], p < 0.001), but IDE mRNA and enzyme activity had no significant difference (SMD = 0.02, 95% CI [-0.40, 0.43] and SMD = 0.06, 95% CI [-0.41, 0.53] respectively). Subgroup analyses found that IDE protein level was decreased in both cortex and hippocampus of AD cases (SMD = -0.43, 95% CI [-0.71, -0.16], p = 0.002 and SMD = -0.53, 95% CI [-0.91, -0.15], p = 0.006 respectively). However, IDE mRNA was higher in cortex of AD cases (SMD = 0.71, 95% CI [0.14, 1.29], p = 0.01), not in hippocampus (SMD = -0.26, 95% CI [-0.58, 0.06]). Conclusions: Our results indicate that AD patients may have lower IDE protease level. Further relevant studies are still needed to verify whether IDE is one of the factors affecting Aβ abnormal accumulation and throw new insights for AD detection or therapy.

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Biological Signatures of Alzheimer’s Disease

Current Topics in Medicinal Chemistry ◽

10.2174/1568026620666200228095553 ◽

2020 ◽

Vol 20 (9) ◽

pp. 770-781 ◽

Cited By ~ 12

Author(s):

Poornima Sharma ◽

Anjali Sharma ◽

Faizana Fayaz ◽

Sharad Wakode ◽

Faheem H. Pottoo

Keyword(s):

Alzheimer’S Disease ◽

Alzheimer's Disease ◽

White Matter ◽

Senile Plaque ◽

Senile Plaques ◽

Amyloid Deposition ◽

Immune Defense ◽

Amyloid Angiopathy ◽

Microvascular Changes ◽

Β Amyloid

Alzheimer’s disease (AD) is the most prevalent and severe neurodegenerative disease affecting more than 0.024 billion people globally, more common in women as compared to men. Senile plaques and amyloid deposition are among the main causes of AD. Amyloid deposition is considered as a central event which induces the link between the production of β amyloid and vascular changes. Presence of numerous biomarkers such as cerebral amyloid angiopathy, microvascular changes, senile plaques, changes in white matter, granulovascular degeneration specifies the manifestation of AD while an aggregation of tau protein is considered as a primary marker of AD. Likewise, microvascular changes, activation of microglia (immune defense system of CNS), amyloid-beta aggregation, senile plaque and many more biomarkers are nearly found in all Alzheimer’s patients. It was seen that 70% of Alzheimer’s cases occur due to genetic factors. It has been reported in various studies that apolipoprotein E(APOE) mainly APOE4 is one of the major risk factors for the later onset of AD. Several pathological changes also occur in the white matter which include dilation of the perivascular space, loss of axons, reactive astrocytosis, oligodendrocytes and failure to drain interstitial fluid. In this review, we aim to highlight the various biological signatures associated with the AD which may further help in discovering multitargeting drug therapy.

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Senile plaque calcification of the lamina circumvoluta medullaris in Alzheimer's disease

Neuropathology ◽

10.1111/neup.12742 ◽

2021 ◽

Author(s):

Ralf Schober ◽

Isabel Hilbrich ◽

Carsten Jäger ◽

Max Holzer

Keyword(s):

Alzheimer’S Disease ◽

Alzheimer's Disease ◽

Senile Plaque

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Biophysical insights into the membrane interaction of the core amyloid-forming Aβ40fragment K16–K28 and its role in the pathogenesis of Alzheimer's disease

Physical Chemistry Chemical Physics ◽

10.1039/c6cp02023b ◽

2016 ◽

Vol 18 (25) ◽

pp. 16890-16901 ◽

Cited By ~ 10

Author(s):

Swapna Bera ◽

Kyle J. Korshavn ◽

Rajiv K. Kar ◽

Mi Hee Lim ◽

Ayyalusamy Ramamoorthy ◽

...

Keyword(s):

Alzheimer’S Disease ◽

Alzheimer's Disease ◽

Hydrophobic Region ◽

Membrane Interaction ◽

The Core

Role of central hydrophobic region of Aβ40 in membrane interaction.

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Caspase-1/IL-1β represses membrane transport of GluA1 by inhibiting the interaction between Stargazin and GluA1 in Alzheimer’s disease

Molecular Medicine ◽

10.1186/s10020-021-00273-8 ◽

2021 ◽

Vol 27 (1) ◽

Author(s):

Xunhu Gu ◽

Hanjun Wu ◽

Yuqin Xie ◽

Lijun Xu ◽

Xu Liu ◽

...

Keyword(s):

Alzheimer’S Disease ◽

Alzheimer's Disease ◽

Membrane Transport ◽

Learning And Memory ◽

Spatial Learning ◽

Senile Plaque ◽

Spatial Learning And Memory ◽

Memory Ability ◽

Caspase 1 ◽

Plaque Deposition

Abstract Background Alzheimer's disease is a neurodegenerative disease. Previous study has reported that caspase-1/IL-1β is closely associated with Alzheimer's disease. However, the biological role of caspase-1/IL-1β in Alzheimer's disease has not been fully elucidated. This study aimed to explore the mechanism of action of caspase-1/IL-1β in Alzheimer's disease. Methods Mouse hippocampal neurones were treated with Aβ1-42 to induce Alzheimer's disease cell model. APP/PS1 mice and Aβ1-42-induced hippocampal neurones were treated with AC-YVAD-CMK (caspase-1 inhibitor). Spatial learning and memory ability of mice were detected by morris water maze. Flow cytometry, TUNEL staining, Thioflavin S staining and immunohistochemistry were performed to examine apoptosis and senile plaque deposition. Enzyme linked immunosorbent assay and western blot were performed to assess the levels of protein or cytokines. Co-Immunoprecipitation was performed to verify the interaction between Stargazin and GluA1. Results AC-YVAD-CMK treatment improved spatial learning and memory ability and reduced senile plaque deposition of APP/PS1 mice. Moreover, AC-YVAD-CMK promoted membrane transport of GluA1 in APP/PS1 mice. In vitro, Aβ1-42-induced hippocampal neurones exhibited an increase in apoptosis and a decrease in the membrane transport of GluA1, which was abolished by AC-YVAD-CMK treatment. In addition, Stargazin interacted with GluA1, which was repressed by caspase-1. Caspase-1/IL-1β inhibited membrane transport of GluA1 by inhibiting the interaction between Stargazin and GluA1. Conclusions Our data demonstrate that caspase-1/IL-1β represses membrane transport of GluA1 by inhibiting the interaction between Stargazin in Alzheimer's disease. Thus, caspase-1/IL-1β may be a target for Alzheimer's disease treatment.

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Anticholinergics and Benzodiazepines on Cognitive Impairment among Elderly with Alzheimer’s Disease: a One year Follow-Up Study

10.21203/rs.2.17956/v1 ◽

2019 ◽

Author(s):

Rewadee Jenraumjit ◽

Surarong Chinwong ◽

Dujrudee Chinwong ◽

Tipaporn Kanjanarach ◽

Thanat Kshetradat ◽

...

Keyword(s):

Alzheimer’S Disease ◽

Older Adults ◽

Alzheimer's Disease ◽

Cognitive Impairment ◽

Psychological Symptoms ◽

Esterase Inhibitors ◽

One Year ◽

State Examination ◽

Harmful Effects

Abstract Objective Age-associated decline in central cholinergic activity makes older adults susceptible to harmful effects of anticholinergics (ACs). Evidence exists of an association between effects of AC medications on cognition. This retrospective cohort study examines how ACs affect cognition among older adults with Alzheimer’s disease (AD) who received acetylcholine esterase inhibitors (AChEIs) over the course of 12 months. Results A total of 133 (80% women, mean age 78.38 years, SD 7.4) were recruited. No difference in sex, age and comorbid diseases was observed between participants who took ACs, Benzodiazepines (BZDs) and AChEIs. The most common prescribed ACs was quetiapine, being used for behavioral and psychological symptoms (BPSD). Multilevel analysis showed that the change of mental state examination scores were significantly predicted in the group using ACs (t (169), -2.52, p = .020) but not with the groups using BZD (t (162), 0.84, p = .440). Evidence showed that older adults with Alzheimer’s disease and exposed to ACs exhibited lower global cognitive scores than those without AC exposure. Using ACs could be a trade-off between controlling BPSD and aggravating cognitive impairment. Highlighting the awareness of the potential anticholinergic effect is important and may be the best policy.

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Suicide risk within one year of cognitive impairment diagnosis in older adults: a nationwide retrospective cohort study

10.21203/rs.2.19129/v1 ◽

2019 ◽

Author(s):

Jae Woo Choi ◽

Kang Soo Lee ◽

Euna Han

Keyword(s):

Alzheimer’S Disease ◽

Older Adults ◽

Alzheimer's Disease ◽

Cognitive Impairment ◽

Mental Disorders ◽

Suicide Risk ◽

Proportional Hazards ◽

Cox Proportional Hazards ◽

Cox Proportional Hazards Models ◽

One Year

Abstract Background This study aims to investigate suicide risk within one year of receiving a diagnosis of cognitive impairment in older adults without mental disorders. Methods This study used National Health Insurance Service-Senior Cohort data on older adults with newly diagnosed cognitive impairment including Alzheimer’s disease, vascular dementia, other/unspecified dementia, and mild cognitive impairment from 2004 to 2012. We selected 41,195 older adults without cognitive impairment through 1:1 propensity score matching using age, gender, Charlson Comorbidity Index, and index year, with follow-up throughout 2013. We eliminated subjects with mental disorders and estimated adjusted hazard ratios (AHR) of suicide deaths within one year after diagnosis using the Cox proportional hazards models. Results We identified 49 suicide deaths during the first year after cognitive impairment diagnosis. The proportion of observed suicide deaths was the highest within one year after cognitive impairment diagnosis (48.5% of total); older adults with cognitive impairment were at a higher suicide risk than those without cognitive impairment (AHR, 1.89; 95% confidence interval [CI], 1.18–3.04). Subjects with Alzheimer’s disease and other/unspecified dementia were at greater suicide risk than those without cognitive impairment (AHR, 1.94, 1.94; 95% CI, 1.12–3.38, 1.05–3.58). Suicide risk in female and young-old adults (60–74 years) with cognitive impairment was higher than in the comparison group (AHR, 2.61, 5.13; 95% CI, 1.29–5.28, 1.48–17.82). Conclusions Older patients with cognitive impairment were at increased suicide risk within one year of diagnosis. Early intervention for suicide prevention should be provided to older adults with cognitive impairment.

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The Role of APP O-Glycosylation in Alzheimer’s Disease

Biomolecules ◽

10.3390/biom10111569 ◽

2020 ◽

Vol 10 (11) ◽

pp. 1569

Author(s):

Keiko Akasaka-Manya ◽

Hiroshi Manya

Keyword(s):

Alzheimer’S Disease ◽

Alzheimer's Disease ◽

Senile Plaque ◽

Amyloid Β ◽

Pathological Feature ◽

People With Dementia ◽

New Findings ◽

Neurodegenerative Dementia ◽

Aβ Production

The number of people with dementia is increasing rapidly due to the increase in the aging population. Alzheimer’s disease (AD) is a type of neurodegenerative dementia caused by the accumulation of abnormal proteins. Genetic mutations, smoking, and several other factors have been reported as causes of AD, but alterations in glycans have recently been demonstrated to play a role in AD. Amyloid-β (Aβ), a cleaved fragment of APP, is the source of senile plaque, a pathological feature of AD. APP has been reported to undergo N- and O-glycosylation, and several Polypeptide N-acetylgalactosaminyltransferases (ppGalNAc-Ts) have been shown to have catalytic activity for the transfer of GalNAc to APP. Since O-glycosylation in the proximity of a cleavage site in many proteins has been reported to be involved in protein processing, O-glycans may affect the cleavage of APP during the Aβ production process. In this report, we describe new findings on the O-glycosylation of APP and Aβ production.

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