scholarly journals Platycodon grandiflorum Root Protects against Aβ-Induced Cognitive Dysfunction and Pathology in Female Models of Alzheimer’s Disease

Antioxidants ◽  
2021 ◽  
Vol 10 (2) ◽  
pp. 207
Author(s):  
Yunkwon Nam ◽  
Soo Jung Shin ◽  
Yong Ho Park ◽  
Min-Jeong Kim ◽  
Seong Gak Jeon ◽  
...  
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Cognitive Impairment ◽  
Cognitive Dysfunction ◽  
Hippocampal Neurons ◽  
Hippocampal Formation ◽  
Histopathological Analysis ◽  
Root Extract ◽  
Platycodon Grandiflorum ◽  
5Xfad Mice

Alzheimer’s disease (AD) is a devastating neurodegenerative disease characterized by irreversible cognitive dysfunction. Amyloid beta (Aβ) peptide is an important pathological factor that triggers the progression of AD through accumulation and aggregation, which leads to AD-related pathologies that consequently affect cognitive functions. Interestingly, several studies have reported that Platycodon grandiflorum root extract (PGE), besides exhibiting other bioactive effects, displays neuroprotective, anti-neuroinflammatory, and cognitive-enhancing effects. However, to date, it is not clear whether PGE can affect AD-related cognitive dysfunction and pathogenesis. Therefore, to investigate whether PGE influences cognitive impairment in an animal model of AD, we conducted a Y-maze test using a 5XFAD mouse model. Oral administration of PGE for 3 weeks at a daily dose of 100 mg/kg significantly ameliorated cognitive impairment in 5XFAD mice. Moreover, to elucidate the neurohistological mechanisms underlying the PGE-mediated alleviative effect on cognitive dysfunction, we performed histological analysis of hippocampal formation in these mice. Histopathological analysis showed that PGE significantly alleviated AD-related pathologies such as Aβ accumulation, neurodegeneration, oxidative stress, and neuroinflammation. In addition, we observed a neuroprotective and antioxidant effect of PGE in mouse hippocampal neurons. Our findings suggest that administration of PGE might act as one of the therapeutic agents for AD by decreasing Aβ related pathology and ameliorating Aβ induced cognitive impairment.

Lipidomics and cognitive dysfunction – A Narrative review

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.

DEF8 and Autophagy-Associated Genes are Altered in Mild Cognitive Impairment, Probable Alzheimer’s Disease Patients and a Transgenic Model of the Disease

2021 ◽  
pp. 1-16
Author(s):  
Esteban Leyton ◽  
Diego Matus ◽  
Sandra Espinoza ◽  
José Matías Benitez ◽  
Bastián I. Cortes ◽  
...  
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Cognitive Impairment ◽  
Mild Cognitive Impairment ◽  
Real Time ◽  
Real Time Pcr ◽  
Mononuclear Cells ◽  
Differentially Expressed ◽  
Protein Levels ◽  
5Xfad Mice

Background: Disturbances in the autophagy/endolysosomal systems are proposed as early signatures of Alzheimer’s disease (AD). However, few studies are available concerning autophagy gene expression in AD patients. Objective: To explore the differential expression of classical genes involved in the autophagy pathway, among them a less characterized one, DEF8 (Differentially expressed in FDCP 8), initially considered a Rubicon family member, in peripheral blood mononuclear cells (PBMCs) from individuals with mild cognitive impairment (MCI) and probable AD (pAD) and correlate the results with the expression of DEF8 in the brain of 5xFAD mice. Method: By real-time PCR and flow cytometry, we evaluated autophagy genes levels in PBMCs from MCI and pAD patients. We evaluated DEF8 levels and its localization in brain samples of the 5xFAD mice by real-time PCR, western blot, and immunofluorescence. Results: Transcriptional levels of DEF8 were significantly reduced in PBMCs of MCI and pAD patients compared with healthy donors, correlating with the MoCA and MoCA-MIS cognitive tests scores. DEF8 protein levels were increased in lymphocytes from MCI but not pAD, compared to controls. In the case of brain samples from 5xFAD mice, we observed a reduced mRNA expression and augmented protein levels in 5xFAD compared to age-matched wild-type mice. DEF8 presented a neuronal localization. Conclusion: DEF8, a protein proposed to act at the final step of the autophagy/endolysosomal pathway, is differentially expressed in PBMCs of MCI and pAD and neurons of 5xFAD mice. These results suggest a potential role for DEF8 in the pathophysiology of AD.

scholarly journals RTP801/REDD1 contributes to neuroinflammation severity and memory impairments in Alzheimer’s disease

2021 ◽  
Vol 12 (6) ◽  
Author(s):  
Leticia Pérez-Sisqués ◽  
Anna Sancho-Balsells ◽  
Júlia Solana-Balaguer ◽  
Genís Campoy-Campos ◽  
Marcel Vives-Isern ◽  
...  
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Hippocampal Neurons ◽  
Mrna Levels ◽  
Spine Density ◽  
Memory Impairments ◽  
Protein Levels ◽  
Synaptic Markers ◽  
5Xfad Mice

AbstractRTP801/REDD1 is a stress-regulated protein whose upregulation is necessary and sufficient to trigger neuronal death. Its downregulation in Parkinson’s and Huntington’s disease models ameliorates the pathological phenotypes. In the context of Alzheimer’s disease (AD), the coding gene for RTP801, DDIT4, is responsive to Aβ and modulates its cytotoxicity in vitro. Also, RTP801 mRNA levels are increased in AD patients’ lymphocytes. However, the involvement of RTP801 in the pathophysiology of AD has not been yet tested. Here, we demonstrate that RTP801 levels are increased in postmortem hippocampal samples from AD patients. Interestingly, RTP801 protein levels correlated with both Braak and Thal stages of the disease and with GFAP expression. RTP801 levels are also upregulated in hippocampal synaptosomal fractions obtained from murine 5xFAD and rTg4510 mice models of the disease. A local RTP801 knockdown in the 5xFAD hippocampal neurons with shRNA-containing AAV particles ameliorates cognitive deficits in 7-month-old animals. Upon RTP801 silencing in the 5xFAD mice, no major changes were detected in hippocampal synaptic markers or spine density. Importantly, we found an unanticipated recovery of several gliosis hallmarks and inflammasome key proteins upon neuronal RTP801 downregulation in the 5xFAD mice. Altogether our results suggest that RTP801 could be a potential future target for theranostic studies since it could be a biomarker of neuroinflammation and neurotoxicity severity of the disease and, at the same time, a promising therapeutic target in the treatment of AD.

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

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

scholarly journals Biomarkers of vascular cognitive impairment

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.

scholarly journals Treatment of canine cognitive dysfunction with novel butyrylcholinesterase inhibitor

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.

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

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.

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 ◽  
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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