F1000Prime recommendation of Alzheimer's Disease-Associated β-Amyloid Is Rapidly Seeded by Herpesviridae to Protect against Brain Infection.

This study presents the synthesis of binary tetrohydro-γ-carbolines with ditriazol spacers of varying length, which exhibit anticholinesterase and antioxidant activity, as compared to the original Dimebon prototype. Anticholinesterase activity suggests the potential ability of the new compounds to block β-amyloid aggregation induced by anticholinesterase, making them promising candidates for further research preparations for the treatment of Alzheimer's disease. Particular attention should be paid to the conjugate with an intertriazol hexamethylene spacer, which can be regarded as the leading compound in this series.

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Alzheimer’s Disease: Erythrocyte 2,3-diphosphoglycerate Content and Circulating Erythropoietin

Current Alzheimer Research ◽

10.2174/1567205016666190827120108 ◽

2019 ◽

Vol 16 (9) ◽

pp. 834-835

Author(s):

Petter Järemo ◽

Alenka Jejcic ◽

Vesna Jelic ◽

Tasmin Shahnaz ◽

Homira Behbahani ◽

...

Keyword(s):

Alzheimer’S Disease ◽

Alzheimer's Disease ◽

Cognitive Impairment ◽

Cell Damage ◽

Control Group ◽

Red Cell ◽

Oxygen Release ◽

Regulatory Pathways ◽

Β Amyloid ◽

2,3 Dpg

Background: Alzheimer’s Disease (AD) features the accumulation of β-amyloid in erythrocytes. The subsequent red cell damage may well affect their oxygen-carrying capabilities. 2,3- diphosphoglycerate (2,3-DPG) binds to the hemoglobin thereby promoting oxygen release. It is theorized that 2,3-DPG is reduced in AD and that the resulting hypoxia triggers erythropoietin (EPO) release. Methods & Objective: To explore this theory, we analyzed red cell 2,3-DPG content and EPO in AD, mild cognitive impairment, and the control group, subjective cognitive impairment. Results: We studied (i) 2,3-DPG in red cells, and (ii) circulating EPO in AD, and both markers were unaffected by dementia. Disturbances of these oxygen-regulatory pathways do not appear to participate in brain hypoxia in AD.

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Synthesis of a Novel Curcumin Derivative as a Potential Imaging Probe in Alzheimer’s Disease Imaging

Current Alzheimer Research ◽

10.2174/1567205016666190816130516 ◽

2019 ◽

Vol 16 (8) ◽

pp. 723-731 ◽

Cited By ~ 1

Author(s):

Alexander Sturzu ◽

Sumbla Sheikh ◽

Hubert Kalbacher ◽

Thomas Nägele ◽

Christopher Weidenmaier ◽

...

Keyword(s):

Alzheimer’S Disease ◽

Alzheimer's Disease ◽

Flow Cytometry ◽

Transgenic Mice ◽

Ex Vivo ◽

Amyloid Plaques ◽

Laser Scanning Microscopy ◽

Β Amyloid ◽

Curcumin Derivative

Background: Curcumin has been of interest in the field of Alzheimer’s disease. Early studies on transgenic mice showed promising results in the reduction of amyloid plaques.However, curcumin is very poorly soluble in aqueous solutions and not easily accessible to coupling as it contains only phenolic groups as potential coupling sites. For these reasons only few imaging studies using curcumin bound as an ester were performed and curcumin is mainly used as nutritional supplement. Methods: In the present study we produced an aminoethyl ether derivative of curcumin using a nucleophilic substitution reaction. This is a small modification and should not impact the properties of curcumin while introducing an easily accessible reactive amino group. This novel compound could be used to couple curcumin to other molecules using the standard methods of peptide synthesis. We studied the aminoethyl-curcumin compound and a tripeptide carrying this aminoethyl-curcumin and the fluorescent dye fluorescein (FITC-curcumin) in vitro on cell culture using confocal laser scanning microscopy and flow cytometry. Then these two substances were tested ex vivo on brain sections prepared from transgenic mice depicting Alzheimer-like β-amyloid plaques. Results: In the in vitro CLSM microscopy and flow cytometry experiments we found dot-like unspecific uptake and only slight cytotoxicity correlating with this uptake. As these measurements were optimized for the use of fluorescein as dye we found that the curcumin at 488nm fluorescence excitation was not strong enough to use it as a fluorescence marker in these applications. In the ex vivo sections CLSM experiments both the aminoethyl-curcumin and the FITC-curcumin peptide bound specifically to β- amyloid plaques. Conclusion: In conclusion we successfully produced a novel curcumin derivative which could easily be coupled to other imaging or therapeutic molecules as a sensor for amyloid plaques.

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MiR-335-5p Inhibits β-Amyloid (Aβ) Accumulation to Attenuate Cognitive Deficits Through Targeting c-jun-N-terminal Kinase 3 in Alzheimer’s Disease

Current Neurovascular Research ◽

10.2174/1567202617666200128141938 ◽

2020 ◽

Vol 17 (1) ◽

pp. 93-101 ◽

Cited By ~ 3

Author(s):

Dan Wang ◽

Zhifu Fei ◽

Song Luo ◽

Hai Wang

Keyword(s):

Alzheimer’S Disease ◽

Alzheimer's Disease ◽

Transgenic Mice ◽

Western Blot ◽

Mrna Expression ◽

Cognitive Deficits ◽

Protein Levels ◽

Amyloid Aβ ◽

Β Amyloid ◽

The Relationship

Objectives: Alzheimer's disease (AD), also known as senile dementia, is a common neurodegenerative disease characterized by progressive cognitive impairment and personality changes. Numerous evidences have suggested that microRNAs (miRNAs) are involved in the pathogenesis and development of AD. However, the exact role of miR-335-5p in the progression of AD is still not clearly clarified. Methods: The protein and mRNA levels were measured by western blot and RNA extraction and quantitative real-time PCR (qRT-PCR), respectively. The relationship between miR-335-5p and c-jun-N-terminal kinase 3 (JNK3) was confirmed by dual-luciferase reporter assay. SH-SY5Y cells were transfected with APP mutant gene to establish the in vitro AD cell model. Flow cytometry and western blot were performed to evaluate cell apoptosis. The APP/PS1 transgenic mice were used as an in vivo AD model. Morris water maze test was performed to assess the effect of miR- 335-5p on the cognitive deficits in APP/PS1 transgenic mice. Results: The JNK3 mRNA expression and protein levels of JNK3 and β-Amyloid (Aβ) were significantly up-regulated, and the mRNA expression of miR-335-5p was down-regulated in the brain tissues of AD patients. The expression levels of miR-335-5p and JNK3 were significantly inversely correlated. Further, the dual Luciferase assay verified the relationship between miR-335- 5p and JNK3. Overexpression of miR-335-5p significantly decreased the protein levels of JNK3 and Aβ and inhibited apoptosis in SH-SY5Y/APPswe cells, whereas the inhibition of miR-335-5p obtained the opposite results. Moreover, the overexpression of miR-335-5p remarkably improved the cognitive abilities of APP/PS1 mice. Conclusion: The results revealed that the increased JNK3 expression, negatively regulated by miR-335-5p, may be a potential mechanism that contributes to Aβ accumulation and AD progression, indicating a novel approach for AD treatment.

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β-Amyloid Fibrillation and/or Hyperhomocysteinemia Modify Striatal Patterns of Hyaluronic Acid and Dermatan Sulfate: Possible Role in the Pathogenesis of Alzheimer's Disease

Current Alzheimer Research ◽

10.2174/1567210198607222050 ◽

2010 ◽

Vol 999 (999) ◽

pp. 1-8

Author(s):

S. Genedani ◽

L. F. Agnati ◽

G. Leo ◽

D. Buzzega ◽

F. Maccari ◽

...

Keyword(s):

Alzheimer’S Disease ◽

Alzheimer's Disease ◽

Hyaluronic Acid ◽

Dermatan Sulfate ◽

Amyloid Fibrillation ◽

Β Amyloid

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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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Continuous and Cyclic Progesterone Differentially Interact with Estradiol in the Regulation of Alzheimer-Like Pathology in Female 3×Transgenic-Alzheimer’s Disease Mice

Endocrinology ◽

10.1210/en.2009-1487 ◽

2010 ◽

Vol 151 (6) ◽

pp. 2713-2722 ◽

Cited By ~ 57

Author(s):

Jenna C. Carroll ◽

Emily R. Rosario ◽

Angela Villamagna ◽

Christian J. Pike

Keyword(s):

Alzheimer’S Disease ◽

Alzheimer's Disease ◽

Postmenopausal Women ◽

Transgenic Mouse Model ◽

Dependent Behavior ◽

Potential Efficacy ◽

Increased Risk ◽

Neural Interactions ◽

Β Amyloid ◽

Insight Into

Depletion of estrogens and progesterone at menopause has been linked to an increased risk for the development of Alzheimer’s disease (AD) in women. A currently controversial literature indicates that although treatment of postmenopausal women with hormone therapy (HT) may reduce the risk of AD, several parameters of HT may limit its potential efficacy and perhaps, even exacerbate AD risk. One such parameter is continuous vs. cyclic delivery of the progestogen component of HT. Recent experimental evidence suggests that continuous progesterone can attenuate neural actions of estradiol (E2). In the present study, we compared the effects of continuous and cyclic progesterone treatment in the presence and absence of E2 in ovariectomized 3×Tg-AD mice, a transgenic mouse model of AD. We found that ovariectomy-induced hormone depletion increases AD-like pathology in female 3×Tg-AD mice, including accumulation of β-amyloid, tau hyperphosphorylation, and impaired hippocampal-dependent behavior. E2 treatment alone prevents the increases in pathology. Continuous progesterone did not affect β-amyloid levels when delivered alone but blocked the Aβ-lowering action of E2. In contrast, cyclic progesterone significantly reduced β-amyloid levels by itself and enhanced rather than inhibited the E2 effects. These results provide new insight into the neural interactions between E2 and progesterone that may prove valuable in optimizing HT regimens in postmenopausal women.

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