Neuroprotective Effects of Salidroside Against Beta-Amyloid-Induced Cognitive Impairment in Alzheimer’s Disease Mice Through the PKC/p38MAPK Pathway

Alzheimer’s disease (AD) is a common neurodegenerative disease as well as the main cause of dementia. A progressive cognitive decline with age is considered as the major manifestation of AD. Amyloid beta-peptide (Aβ) is one of the primary causes leading to cognitive dysfunction in AD. Recent studies have suggested that the activation of PKC/p38MAPK pathway is related to the neurotoxicity induced by β-amyloid. Salidroside is the major active component of Rhodiola crenu-lata, has been reported with widely neuroprotective effects. The protective effects of salidroside against β-amyloid induced neural apoptosis via the MAPKs pathway has been confirmed in the vitro study. The present study aimed to investigate the neuroprotective effects of salidroside through the PKC/p38MAPK pathway in β-amyloid induced AD mice. The results by Y maze showed that salidroside improved Aβ-induced cognitive impairment. Nissl staining results showed that salidroside affected neuronal damage in hippocampus and cerebral cortex of AD mice. Western blot results revealed that salidroside enhanced protein expression of p-PKC, whereas it suppressed protein expression of p-p38MAPK, Bax and cleaved caspase-3. Thus, the present results demonstrated that salidroside ameliorated cognitive dysfunction in Aβ25–35 induced AD mice. And the effects on protein expression of p-PKC and p-p38MAPK contributed to the neuroprotective effects of salidroside against neural apoptosis in AD mice.

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Lipidomics and cognitive dysfunction – A Narrative review

Turkish Journal of Biochemistry ◽

10.1515/tjb-2020-0134 ◽

2020 ◽

Vol 45 (2) ◽

Author(s):

Arpita Chakraborty ◽

Samir Kumar Praharaj ◽

R. V. Krishnananda Prabhu ◽

M. Mukhyaprana Prabhu

Keyword(s):

Alzheimer’S Disease ◽

Alzheimer's Disease ◽

Cognitive Impairment ◽

Vascular Dementia ◽

Cognitive Dysfunction ◽

Neurological Disorders ◽

Brain Lipids ◽

Complex Lipids ◽

Functional Components ◽

The Brain

AbstractBackgroundMore than half portion of the brain is formed by lipids. They play critical roles in maintaining the brain's structural and functional components. Any dysregulation in these brain lipids can lead to cognitive dysfunction which are associated with neurological disorders such as Alzheimer's disease, Parkinson's disease, schizophrenia, vascular dementia etc. Studies have linked lipids with cognitive impairment. But not much has been studied about the complex brain lipids which might play a pivotal role in cognitive impairment. This review aims to highlight the lipidomic profiles in patients with cognitive dysfunction.ResultsForty-five articles were reviewed. These studies show alterations in complex lipids such as sphingolipids, phospholipids, glycolipids and sterols in brain in various neurological disorders such as vascular dementia, Parkinson's and Alzheimer's disease. However, the classes of fatty acids in these lipids involved are different across studies.ConclusionsThere is a need for targeted lipidomics analysis, specifically including sphingolipids in patients with neurodegenerative disorders so as to improve diagnostics as well as management of these disorders.

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Cognitive impairment and neuronal damage in Alzheimer's disease are malleable

10.17077/etd.ymmea0c4 ◽

2017 ◽

Author(s):

Jaymie Richelle Voorhees

Keyword(s):

Alzheimer’S Disease ◽

Alzheimer's Disease ◽

Cognitive Impairment ◽

Neuronal Damage

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P3-175: Relationships between global cognitive dysfunction and PET biomarkers in normal aging, mild cognitive impairment and Alzheimer's disease

Alzheimer s & Dementia ◽

10.1016/j.jalz.2012.05.1395 ◽

2012 ◽

Vol 8 (4S_Part_14) ◽

pp. P514-P514

Author(s):

Eun Hyun Seo ◽

Dong Young Lee ◽

IL Han Choo ◽

Bo Kyung Sohn ◽

Jee Wook Kim ◽

...

Keyword(s):

Alzheimer’S Disease ◽

Alzheimer's Disease ◽

Cognitive Impairment ◽

Mild Cognitive Impairment ◽

Cognitive Dysfunction ◽

Normal Aging

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Nutrigenomic Studies on the Ameliorative Effect of Enzyme-Digested Phycocyanin in Alzheimer’s Disease Model Mice

Nutrients ◽

10.3390/nu13124431 ◽

2021 ◽

Vol 13 (12) ◽

pp. 4431

Author(s):

Yasuyuki Imai ◽

Yurino Koseki ◽

Makoto Hirano ◽

Shin Nakamura

Keyword(s):

Gene Expression ◽

Alzheimer’S Disease ◽

Alzheimer's Disease ◽

Cognitive Impairment ◽

Oral Administration ◽

Expression Patterns ◽

Disease Model ◽

Neuroprotective Effects ◽

Aberrant Expression ◽

Ameliorative Effect

Alzheimer’s disease (AD) is the most common form of dementia, and the cognitive impairments associated with this degenerative disease seriously affect daily life. Nutraceuticals for the prevention or delay of AD are urgently needed. It has been increasingly observed that phycocyanin (PC) exerts neuroprotective effects. AD model mice intracerebroventricularly injected with amyloid beta-peptide 25–35 (Aβ25–35) at 10 nmol/head displayed significant cognitive impairment in the spontaneous alternation test. Cognitive impairment was significantly ameliorated in mice treated with 750 mg/kg of enzyme-digested (ED) PC by daily oral administration for 22 consecutive days. Application of DNA microarray data on hippocampal gene expression to nutrigenomics studies revealed that oral EDPC counteracted the aberrant expression of 35 genes, including Prnp, Cct4, Vegfd (Figf), Map9 (Mtap9), Pik3cg, Zfand5, Endog, and Hbq1a. These results suggest that oral administration of EDPC ameliorated cognitive impairment in AD model mice by maintaining and/or restoring normal gene expression patterns in the hippocampus.

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Biomarkers of vascular cognitive impairment

CARDIOVASCULAR THERAPY AND PREVENTION ◽

10.15829/1728-8800-2021-2677 ◽

2021 ◽

Vol 20 (3) ◽

pp. 2677

Author(s):

O. V. Zimnitskaya ◽

E. Yu. Mozheyko ◽

M. M. Petrova

Keyword(s):

Alzheimer’S Disease ◽

Alzheimer's Disease ◽

Differential Diagnosis ◽

Cognitive Impairment ◽

Cognitive Dysfunction ◽

Web Of Science ◽

Vascular Cognitive Impairment ◽

Cerebrovascular Diseases ◽

Adequate Treatment ◽

Genetic Biomarkers

There is currently no approved list of vascular cognitive impairment biomarkers. The main problem for the practitioner in identifying cognitive impairment in patients is the differential diagnosis of Alzheimer's disease, vascular cognitive impairment, and other diseases, which are much less common. Vascular cognitive impairment includes post-stroke dementia, cognitive dysfunction in cardio-and cerebrovascular diseases. Without etiology identification, it is impossible to prescribe adequate treatment. Another challenge is identifying cognitive impairment before dementia develops. This literature review is devoted to the search and critical analysis of candidates for biomarkers of vascular cognitive impairment and the establishment of markers of moderate cognitive dysfunction. The papers were searched for in the Web of Science and PubMed databases. A list of cerebrospinal fluid, plasma, serum and genetic biomarkers was made, allowing for differential diagnosis between vascular impairment and Alzheimer's disease. The markers of moderate cognitive dysfunction, which make it possible to identify cognitive impairment at the pre-dementia stage, were also identified.

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Treatment of canine cognitive dysfunction with novel butyrylcholinesterase inhibitor

Scientific Reports ◽

10.1038/s41598-021-97404-2 ◽

2021 ◽

Vol 11 (1) ◽

Author(s):

Maja Zakošek Pipan ◽

Sonja Prpar Mihevc ◽

Malan Štrbenc ◽

Urban Košak ◽

Ilija German Ilić ◽

...

Keyword(s):

Alzheimer’S Disease ◽

Alzheimer's Disease ◽

Cognitive Impairment ◽

Cognitive Dysfunction ◽

Cognitive Abilities ◽

Cognitive Status ◽

Moderate Cognitive Impairment ◽

Interesting Candidate ◽

Butyrylcholinesterase Inhibitor

AbstractCanine cognitive dysfunction (CCD) is common in aged dogs and has many similarities with Alzheimer’s disease. Unfortunately, like Alzheimer’s disease, CCD cannot be cured. In the present study, we treated dogs with CCD with our newly developed and characterized butyrylcholinesterase inhibitor (BChEi). Seventeen dogs were randomized into two groups (treated with BChEi and untreated) and followed for 6 months at regular check-ups. The dogs’ cognitive status was determined by a Canine Dementia Scale (CADES) questionnaire and two cognitive tests. In dogs with moderate cognitive impairment, treatment caused significant improvement in the clinical rating of cognitive abilities and the performance-based tests of cognitive functioning when compared to the untreated group (p < 0.001). Dogs treated with BChEi showed markedly improved cognitive function with enhanced quality of life. No side effects were observed in the treated dogs with moderate cognitive impairment. According to the results of this preliminary study, there is an indication that novel BChEi may be a promising drug for the treatment of CCD in dogs and may be an interesting candidate for the treatment of Alzheimer's disease in humans. However, further clinical studies are needed to confirm this.

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Detection and Prediction of Mild Cognitive Impairment in Alzheimer’s Disease Mice

Journal of Alzheimer s Disease ◽

10.3233/jad-200675 ◽

2020 ◽

Vol 77 (3) ◽

pp. 1209-1221

Author(s):

Surya Prakash Rai ◽

Pablo Bascuñana ◽

Mirjam Brackhan ◽

Markus Krohn ◽

Luisa Möhle ◽

...

Keyword(s):

Alzheimer’S Disease ◽

Alzheimer's Disease ◽

Cognitive Impairment ◽

Mild Cognitive Impairment ◽

Cognitive Dysfunction ◽

Age Of Onset ◽

Amyloid Β ◽

Current Approach ◽

Classification Algorithm ◽

Wild Type

Background: The recent failure of clinical trials to treat Alzheimer’s disease (AD) indicates that the current approach of modifying disease is either wrong or is too late to be efficient. Mild cognitive impairment (MCI) denotes the phase between the preclinical phase and clinical overt dementia. AD mouse models that overexpress human amyloid-β (Aβ) are used to study disease pathogenesis and to conduct drug development/testing. However, there is no direct correlation between the Aβ deposition, the age of onset, and the severity of cognitive dysfunction. Objective: To detect and predict MCI when Aβ plaques start to appear in the hippocampus of an AD mouse. Methods: We trained wild-type and AD mice in a Morris water maze (WM) task with different inter-trial intervals (ITI) at 3 months of age and assessed their WM performance. Additionally, we used a classification algorithm to predict the genotype (APPtg versus wild-type) of an individual mouse from their respective WM data. Results: MCI can be empirically detected using a short-ITI protocol. We show that the ITI modulates the spatial learning of AD mice without affecting the formation of spatial memory. Finally, a simple classification algorithm such as logistic regression on WM data can give an accurate prediction of the cognitive dysfunction of a specific mouse. Conclusion: MCI can be detected as well as predicted simultaneously with the onset of Aβ deposition in the hippocampus in AD mouse model. The mild cognitive impairment prediction can be used for assessing the efficacy of a treatment.

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Citicoline in the Treatment of Mild Cognitive Impairment in Blood Relatives of Patients with Alzheimer’s Disease: Immediate and Long-Term Effects of Course Therapy

Psychiatry ◽

10.30629/2618-6667-2021-19-4-42-51 ◽

2021 ◽

Vol 19 (4) ◽

pp. 42-51

Author(s):

N. D. Seleznеva ◽

I. F. Roshchina ◽

E. V. Ponomareva ◽

S. Iv. Gavrilova

Keyword(s):

Alzheimer’S Disease ◽

Alzheimer's Disease ◽

Cognitive Impairment ◽

Mild Cognitive Impairment ◽

Cognitive Functioning ◽

Cognitive Dysfunction ◽

Therapeutic Effects ◽

Long Term Effects ◽

Voluntary Attention

The aim was to study immediate and long-term (post-therapeutic) effects of a three-month course of therapy with citicoline in 1st-degree relatives of patients with Alzheimer’s disease (AD). All the included relatives of patients with AD revealed signs of minimal cognitive dysfunction (MCD) and mild cognitive decline syndrome (MCI — Mild Cognitive Impairment, ICD-10 code F06.7). Study participants: the study involved 90 first-degree relatives: 24 with MCI and 66 with MCD. Study design: an open-label comparative multidisciplinary study of the six-month dynamics of cognitive functioning of two groups of relatives who received a three-month course of citicoline therapy. The baseline indicators of the cognitive functioning of relatives with MCI syndrome and MKD were compared with the indicators at the end of the three-month course of therapy with citicoline at a daily dose of 1000 mg as well as 3 months after the end of the course of treatment. Methods: clinical, psychopathological, neuropsychological, psychometric, genetic, statistical ones. Results: а significant positive effect of the course therapy with citicoline on the cognitive impairment of 1st degree AD-patients’ relatives with minimal cognitive dysfunction and more pronounced cognitive impairments met the diagnostic criteria for MCI syndrome has been found. A significantly greater value of both immediate and long-term therapeutic effect of MKD compared with MCI in relatives was established by psychometric and neuropsychological indicators characterizing voluntary memorization of verbal and visual stimuli, optical and spatial activity, voluntary attention, and associative verbal thinking. Conclusion: the results of the study can be used as the basis for a model of prevention of the progression of cognitive deficit and the development of dementia in persons with a high risk of developing AD, i.e. in individuals with both genetic risk and signs of cognitive impairment.

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Abnormalities of Cortical Sources of Resting State Alpha Electroencephalographic Rhythms are Related to Education Attainment in Cognitively Unimpaired Seniors and Patients with Alzheimer’s Disease and Amnesic Mild Cognitive Impairment

Cerebral Cortex ◽

10.1093/cercor/bhaa356 ◽

2020 ◽

Author(s):

Claudio Babiloni ◽

Raffaele Ferri ◽

Giuseppe Noce ◽

Roberta Lizio ◽

Susanna Lopez ◽

...

Keyword(s):

Alzheimer’S Disease ◽

Alzheimer's Disease ◽

Cognitive Impairment ◽

Mild Cognitive Impairment ◽

Resting State ◽

Compensatory Mechanisms ◽

Neuroprotective Effects ◽

Diagnostic Biomarkers ◽

Cortical Sources ◽

Gender And Education

Abstract In normal old (Nold) and Alzheimer’s disease (AD) persons, a high cognitive reserve (CR) makes them more resistant and resilient to brain neuropathology and neurodegeneration. Here, we tested whether these effects may affect neurophysiological oscillatory mechanisms generating dominant resting state electroencephalographic (rsEEG) alpha rhythms in Nold and patients with mild cognitive impairment (MCI) due to AD (ADMCI). Data in 60 Nold and 70 ADMCI participants, stratified in higher (Edu+) and lower (Edu–) educational attainment subgroups, were available in an Italian–Turkish archive. The subgroups were matched for age, gender, and education. RsEEG cortical sources were estimated by eLORETA freeware. As compared to the Nold-Edu– subgroup, the Nold-Edu+ subgroup showed greater alpha source activations topographically widespread. On the contrary, in relation to the ADMCI-Edu– subgroup, the ADMCI-Edu+ subgroup displayed lower alpha source activations topographically widespread. Furthermore, the 2 ADMCI subgroups had matched cerebrospinal AD diagnostic biomarkers, brain gray–white matter measures, and neuropsychological scores. The current findings suggest that a high CR may be related to changes in rsEEG alpha rhythms in Nold and ADMCI persons. These changes may underlie neuroprotective effects in Nold seniors and subtend functional compensatory mechanisms unrelated to brain structure alterations in ADMCI patients.

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