scholarly journals A Maitake (Grifola frondosa) polysaccharide ameliorates Alzheimer's disease-like pathology and cognitive impairments by enhancing microglial amyloid-β clearance

RSC Advances ◽  
2019 ◽  
Vol 9 (64) ◽  
pp. 37127-37135
Author(s):  
Yao Bai ◽  
Lingling Chen ◽  
Yao Chen ◽  
Xinmeng Chen ◽  
Yilong Dong ◽  
...  
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Cognitive Impairments ◽  
Amyloid Β ◽  
Grifola Frondosa

PGM ameliorates AD-like pathology and cognitive impairments by enhancing microglial amyloid-β clearance.

scholarly journals PGRN Alleviates Cerebral Amyloid-β Burden and Cognitive Impairments via Mediating Neuroinflammation

2020 ◽  
Author(s):  
Wei Xu ◽  
Chen-Chen Tan ◽  
Xi-Peng Cao ◽  
Jin-Tai Yu ◽  
Lan Tan
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Cognitive Impairments ◽  
Clinical Stage ◽  
Amyloid Β ◽  
Mediation Effects ◽  
Mediation Analyses ◽  
Amyloid Aβ ◽  
Β Amyloid ◽  
Tgf Β1

Abstract Background: Both progranulin (PGRN) and neuroinflammatory activities increased over the course of Alzheimer’s disease (AD). In this study, we set out to determine if cerebrospinal fluid (CSF) PGRN could be a marker of neuroinflammation, and if so, how it contributed to AD pathogenesis and cognitive impairments. Methods: A total of 965 participants from the Alzheimer's Disease Neuroimaging Initiative (ADNI) were grouped within the framework of A-T-N biomarker profile and clinical stage. Causal mediation analyses with 10,000 bootstrapped iterations were conducted to explore the mediation effects of neuroinflammatory markers on the associations of PGRN with amyloid burden indicated by CSF β-amyloid (Aβ) levels. The longitudinal influences of PGRN on cognition were tested. Results: Increases of CSF PGRN and multiple neuroinflammatory markers (sTNFR1, sTNFR2, TGF-β1, VCAM1, and ICAM1) were associated with tau-related neurodegeneration, but not with Aβ pathology. PGRN was positively linked with these neuroinflammatory markers only in the presence of tau pathologies (TN+). In TN+ profile, PGRN was associated with higher CSF Aβ42 via mediating neuroinflammatory markers and could also predict slower cognitive decline. The abovementioned associations became non-significant in TN- profile. Conclusions: PGRN could protect against Aβ pathology and cognitive impairments via modulating neuroinflammation that occurs with neuronal injuries.

scholarly journals Relationship between Persistent Dizziness and Markers of Alzheimer's disease – Mayo Clinic Study of Aging

2021 ◽  
Author(s):  
RAZAN AL FAKIR
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Sex Education ◽  
Mayo Clinic ◽  
Cognitive Impairments ◽  
Neuropsychiatric Symptoms ◽  
Amyloid Β ◽  
Density Lipoprotein ◽  
Contributing Factors ◽  
Clinic Study

Abstract Persistent dizziness or lightheadedness ranks among the most frequent complaints in primary care. Persistent dizziness is frequently described as a consequence or side effect of defined entities such as cardiovascular, infectious, neurological, and otological disease. Persistent dizziness is potentially disabling and has a distinct impact on participation, psychosocial interaction, and quality of life. We examined the relationship between persistent dizziness or lightheadedness and Alzheimer's disease (AD) markers among 924 individuals aged ≥50 years (52.3% male, mean age 74 years) selected from 5707 individuals who participated in the population-based Mayo Clinic Study of Aging in Olmsted County, Minnesota. Neuropsychiatric symptoms (depression and anxiety), cognitive evaluation (overall and across multiple domains), magnetic resonance imaging for AD-signature "regional thickness," and 11Carbon-Pittsburgh compound B positron emission tomography (11C-PiB PET) for Amyloid deposition are all investigated. Significant contributing factors to persistent dizziness in older adults were found and include [age, sex (male), lower education, high comorbidity index, high-density lipoprotein, balance problems, neuropsychiatric symptoms, cognitive impairments, and AD-signature” regional thickness]. After adjusting for age, sex, education, medical comorbidities, and other variables, a statistically significant association between persistent dizziness/lightheadedness and neuropsychiatric symptoms, and Amyloid-β deposition. This finding implies that the underlying AD biology may drive both the neuropsychiatric symptoms and persistent dizziness or lightheadedness, even before the onset of cognitive impairments and dementia. Further studies are needed to support the findings.

Alzheimer's Disease-Like Pathologies and Cognitive Impairments Induced by Formaldehyde in Non-Human Primates

2018 ◽  
Vol 15 (14) ◽  
pp. 1304-1321 ◽  
Author(s):  
Rongwei Zhai ◽  
Joshua Rizak ◽  
Na Zheng ◽  
Xiaping He ◽  
Zhenhui Li ◽  
...  
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Tau Protein ◽  
Spatial Working Memory ◽  
Cognitive Impairments ◽  
Neurofibrillary Tangle ◽  
Amyloid Β ◽  
Histopathological Analysis ◽  
Related Factor ◽  
Age Related

Background: Formaldehyde (FA) has been implicated in Alzheimer’s disease (AD) pathology as an age-related factor and as a protein cross-linker known to aggregate Amyloid-Beta (Aβ) and tau protein in vitro. Higher levels of FA have also been found in patients with greater cognitive impairment and in AD patient brains. Objective: To directly evaluate the effect of chronically elevated FA levels on the primate brain with respect to AD pathological markers. Method: Young rhesus macaques (5-8 yrs, without AD related mutations) were given chronic intracerebroventricular (i.c.v.) injections of FA or vehicle over a 12-month period. Monkeys were monitored for changes in cognitive ability and evaluated post-mortem for common AD pathological markers. Results: Monkeys injected with FA were found to have significant spatial working memory impairments. Histopathological analysis revealed the presence of amyloid-β+ neuritic-like plaques, neurofibrillary tangle-like formations, increased tau protein phosphorylation, neuronal loss and reactive gliosis in three memory (and AD) related brain areas (the hippocampus, entorhinal cortex and prefrontal cortex (PFC)) of monkeys receiving i.c.v. injections of FA. ELISA assays revealed that the amounts of pT181 and Aβ42 were markedly higher in the PFC and hippocampus of FA treated monkeys. Conclusion: FA was found to induce major AD-like pathological markers and cognitive impairments in young rhesus monkeys independent of genetic predispositions. This suggests FA may play a significant role in the initiation and progression of the disease.

scholarly journals Pgrn Alleviates Cerebral Amyloid-β Burden and Cognitive Impairments via Mediating Neuroinflammation

2020 ◽  
Author(s):  
Wei Xu ◽  
Chen-Chen Tan ◽  
Xi-Peng Cao ◽  
Jin-Tai Yu ◽  
Lan Tan
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Cognitive Impairments ◽  
Clinical Stage ◽  
Amyloid Β ◽  
Mediation Effects ◽  
Mediation Analyses ◽  
Amyloid Aβ ◽  
Β Amyloid ◽  
Tgf Β1

Abstract Background: Both progranulin (PGRN) and neuroinflammatory activities increased over the course of Alzheimer’s disease (AD). In this study, we set out to determine if cerebrospinal fluid (CSF) PGRN could be a marker of neuroinflammation, and if so, how it contributed to AD pathogenesis and cognitive impairments. Methods: A total of 965 participants from the Alzheimer's Disease Neuroimaging Initiative (ADNI) were grouped within the framework of A-T-N biomarker profile and clinical stage. Causal mediation analyses with 10,000 bootstrapped iterations were conducted to explore the mediation effects of neuroinflammatory markers on the associations of PGRN with amyloid burden indicated by CSF β-amyloid (Aβ) levels. The longitudinal influences of PGRN on cognition were tested. Results: Increases of CSF PGRN and multiple neuroinflammatory markers (sTNFR1, sTNFR2, TGF-β1, VCAM1, and ICAM1) were associated with tau-related neurodegeneration, but not with Aβ pathology. PGRN was positively linked with these neuroinflammatory markers only in the presence of tau pathologies (TN+). In TN+ profile, PGRN was associated with higher CSF Aβ42 via mediating neuroinflammatory markers and could also predict slower cognitive decline. The abovementioned associations became non-significant in TN- profile. Conclusions: PGRN could protect against Aβ pathology and cognitive impairments via modulating neuroinflammation that occurs with neuronal injuries.

Disrupted White Matter Integrity and Cognitive Functions in Amyloid-β Positive Alzheimer’s Disease with Concomitant Lobar Cerebral Microbleeds

2021 ◽  
pp. 1-12
Author(s):  
Yanan Qiao ◽  
Yu Sun ◽  
Jing Guo ◽  
Yaojing Chen ◽  
Wenjie Hou ◽  
...  
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
White Matter ◽  
Fractional Anisotropy ◽  
Cognitive Impairments ◽  
Pearson Correlation ◽  
Amyloid Β ◽  
Cerebral Microbleeds ◽  
Amyloid Pet ◽  
Inferior Longitudinal Fasciculus

Background: Lobar cerebral microbleeds (CMBs), which can impair white matter (WM), are often concomitant with definite Alzheimer’s disease (AD). Objective: To explore the features of cognitive impairments and WM disruptions due to lobar CMBs in patients with AD. Methods: There were 310 participants who underwent Florbetapir F18 (AV45) amyloid PET and susceptibility-weighted imaging. Participants with cognitive impairment and amyloid-β positive (ADCI) were included into three groups: ADCI without CMBs, with strictly lobar CMBs (SL-CMBs), and with mixed CMBs (M-CMBs). Tract-based spatial statistics were performed to detect the group differences in WM integrity. Results: There were 82 patients and 29 healthy controls finally included. A decreasing tendency in memory and executive performance can be found among HCs > no CMBs (n = 16) >SL-CMBs (n = 41) >M-CMBs (n = 25) group. Compared to no CMBs, M-CMBs group had significantly decreased fractional anisotropy in left anterior thalamic radiation (ATR), forceps major, forceps minor and inferior longitudinal fasciculus, bilateral inferior fronto-occipital fasciculus (IFOF), and superior longitudinal fasciculus. M-CMBs group also had lower fractional anisotropy in left ATR, IFOF, uncinate fasciculus, and forceps minor compared with SL-CMBs. Furthermore, analysis of Pearson correlation indicated damages in discrepant WMs were positively associated with impairment of memory, executive function, and attention. Conclusion: This study showed lobar CMBs had intensively aggravated cognitive impairments associated with extensive WM damages in definite AD. These findings highlight that lobar CMBs play an important role in AD progression and need to be taken into consideration for the early detection of AD.

scholarly journals Clausena Harmandiana Root Extract Improved Amyloid-β Induced Cognitive Impairments in Rats By Reducing Aβ1-42 Protein Levels and Neuroinflammation

2022 ◽  
Author(s):  
Nutchareeporn Nillert ◽  
Chantana Boonyarat ◽  
Jariya Umka Welbat ◽  
Komsun Bunreungthong ◽  
Ploenthip Puthongking ◽  
...  
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Recognition Memory ◽  
Normal Saline ◽  
Inflammatory Markers ◽  
Cognitive Impairments ◽  
Amyloid Β ◽  
Root Extract ◽  
Sprague Dawley ◽  
Protein Levels

Abstract Background: Neuroinflammation caused by amyloid‐β (Aβ) is associated with Alzheimer’s disease (AD) pathogenesis. In AD, Aβ accumulation can activate the surrounding microglia which followed by the synthesis and release of pro-inflammatory cytokines, including interleukin-1β (IL-1β) and tumor necrosis factor-α (TNFα), results in cognitive impairments. Clausena harmandiana (CH) is an herb in the Rutaceae family and has been used in folk medicine for the treatment of illness such as stomachache and headache, and as a health tonic. It is interesting that CH root extract (CHRE) exhibits various anti-inflammatory and other pharmacological activities, but there has not been any study in Alzheimer's disease-like animal models.Objectives: This study aimed to investigate the effects of CHRE on Aβ1-42-induced cognitive impairments, increased Aβ1-42 protein levels and neuroinflammation. Methods: Forty-eight adult male Sprague-Dawley rats (250-300 g) were randomly divided into 6 groups (n=8). The rats were given 0.5% sodium carboxymethylcellulose, Celebrex® (10 mg/kg BW) or CHRE (125, 250, and 500 mg/kg BW) and not given any treatment by oral gavage for 35 days. On day 21, all treated rats were injected with aggregated Aβ1-42 at a concentration of 1 µg/µl into both lateral ventricles (1 µl/side), while untreated rats were injected with sterilized normal saline. Ten days later, their recognition memory was assessed using the novel object recognition test. At the end of the experiment, all rats were euthanized by an overdose of thiopental sodium (120 mg/kg BW) and transcardial perfusion with 0.9% normal saline solution, to observe Aβ1-42 protein levels and the expression of inflammatory markers (CD11b-positive microglia, IL-1β, and TNFα) in the cerebral cortex and hippocampus.Results: The results indicated that pretreatment with CHRE at all doses improved impairment of short- and long-term recognition memory. In addition, CHRE significantly decreased Aβ1-42 protein levels and the expression of inflammatory markers in both brain regions as well as pretreatment with Celebrex®.Conclusions: This suggests that CHRE has a potential therapeutic effect against Aβ1-42-induced cognitive impairments by reducing Aβ1-42 protein levels and neuroinflammation.

scholarly journals PGRN alleviates cerebral amyloid-β burden and cognitive impairments via mediating neuroinflammation

2020 ◽  
Author(s):  
Wei Xu ◽  
Chen-Chen Tan ◽  
Xi-Peng Cao ◽  
Jin-Tai Yu ◽  
Lan Tan
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Cognitive Impairments ◽  
Clinical Stage ◽  
Amyloid Β ◽  
Mediation Effects ◽  
Mediation Analyses ◽  
Amyloid Aβ ◽  
Β Amyloid ◽  
Tgf Β1

Abstract Background Both progranulin (PGRN) and neuroinflammatory activities increased over the course of Alzheimer’s disease (AD). In this study, we set out to determine if cerebrospinal fluid (CSF) PGRN could be a marker of neuroinflammation, and if so, how it contributed to AD pathogenesis and cognitive impairments. Methods A total of 965 participants from the Alzheimer's Disease Neuroimaging Initiative (ADNI) were grouped within the framework of A-T-N biomarker profile and clinical stage. Causal mediation analyses with 10,000 bootstrapped iterations were conducted to explore the mediation effects of neuroinflammatory markers on the associations of PGRN with amyloid burden indicated by CSF β-amyloid (Aβ) levels. The longitudinal influences of PGRN on cognition were tested. Results CSF PGRN and multiple neuroinflammatory markers (sTNFR1, sTNFR2, TGF-β1, VCAM1, and ICAM1) were increased with tau-related neurodegeneration. PGRN was positively linked with neuroinflammatory markers associated with tau pathologies (TN+). In TN + population, PGRN was associated with higher CSF Aβ42 via mediating neuroinflammatory markers and could predict slower cognitive decline. The abovementioned associations became non-significant in TN- profile. Conclusions These preliminary findings supported that PGRN could protect against Aβ pathology and cognitive impairments via modulating neuroinflammation that occurs with neuronal injuries.

Amyloid β-peptide and Alzheimer's disease

2014 ◽  
Vol 56 ◽  
pp. 99-110 ◽  
Author(s):  
David Allsop ◽  
Jennifer Mayes
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Senile Plaques ◽  
Strong Support ◽  
Amyloid Β ◽  
Amyloid Β Peptide ◽  
Amyloid Cascade Hypothesis ◽  
Sequence Of Events ◽  
Aβ Amyloid ◽  
Amyloid Cascade

One of the hallmarks of AD (Alzheimer's disease) is the formation of senile plaques in the brain, which contain fibrils composed of Aβ (amyloid β-peptide). According to the ‘amyloid cascade’ hypothesis, the aggregation of Aβ initiates a sequence of events leading to the formation of neurofibrillary tangles, neurodegeneration, and on to the main symptom of dementia. However, emphasis has now shifted away from fibrillar forms of Aβ and towards smaller and more soluble ‘oligomers’ as the main culprit in AD. The present chapter commences with a brief introduction to the disease and its current treatment, and then focuses on the formation of Aβ from the APP (amyloid precursor protein), the genetics of early-onset AD, which has provided strong support for the amyloid cascade hypothesis, and then on the development of new drugs aimed at reducing the load of cerebral Aβ, which is still the main hope for providing a more effective treatment for AD in the future.

Minimalistic Design Approach for Multi-Reactivity against Free Radicals and Metal-Free and Metal-Bound Amyloid-β Peptides: Redox-Based Substitutions of Benzene

2019 ◽  
Author(s):  
Mingeun Kim ◽  
Juhye Kang ◽  
Misun Lee ◽  
Jiyeon Han ◽  
Geewoo Nam ◽  
...  
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Free Radicals ◽  
Amyloid Β ◽  
Design Strategy ◽  
Design Approach ◽  
Metal Free

We report a minimalistic redox-based design strategy for engineering compact molecules based on the simplest aromatic framework, benzene, with multi-reactivity against free radicals, metal-free amyloid-β, and metal-bound amyloid-β, implicated in the most common form of dementia, Alzheimer’s disease.

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