Neurochemical Aspects of Alzheimer’s Disease and Movement Disturbances: A Theory of β-Amyloid and τ-Protein

2018 ◽  
Vol 33 (8) ◽  
pp. 535-540 ◽  
Author(s):  
Auda Fares ◽  
Dieter Borrmann
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Cognitive Impairment ◽  
Cognitive Deficits ◽  
Large Body ◽  
Motor Dysfunction ◽  
Amyloid Aβ ◽  
Β Amyloid ◽  
Τ Protein ◽  
The Relationship

The pathologic and molecular substrate of people diagnosed with cognitive deficits and movement disturbance may not occur exclusively in the context of a brain region, but it may be expressed in another part of body such as muscle. A large body of research has demonstrated that slow motor performance is associated with cognitive impairment in elderly people. The interdependence between motor dysfunction and cognition decline is still not fully understood. Although several factors have been suggested to give a plausible explanation, β-amyloid (Aβ) and τ-protein aggregation is a common feature of a number of neurodegenerative disorders which are characterized by both motor and cognitive impairment, and it is assumed that the aggregation process plays a central role in the pathogenesis of cognitive impairment and motor dysfunction in Alzheimer’s disease. The purpose of the present review is to provide an overview of the available evidence that can help to better elucidate the pathophysiological mechanisms underlying the relationship between cognitive and movement disturbances by focusing on Aβ and τ-protein.

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

2020 ◽  
Vol 17 (1) ◽  
pp. 93-101 ◽  
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.

scholarly journals Plasma β-amyloid in mild behavioural impairment – neuropsychiatric symptoms on the Alzheimer’s continuum

2021 ◽  
Author(s):  
Ruxin Miao ◽  
Hung-Yu Chen ◽  
Sascha Gill ◽  
James Naude ◽  
Eric E. Smith ◽  
...  
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Cognitive Impairment ◽  
Mild Cognitive Impairment ◽  
Neuropsychiatric Symptoms ◽  
Affective Dysregulation ◽  
Prodromal Alzheimer’S Disease ◽  
Amyloid Aβ ◽  
Β Amyloid ◽  
Normal Cognition

AbstractIntroductionSimple markers are required to recognize older adults at higher risk for neurodegenerative disease. Mild behavioural impairment (MBI) and plasma β-amyloid (Aβ) have been independently implicated in the development of incident cognitive decline and dementia. Here we studied the associations between MBI and plasma Aβ42/Aβ40.MethodsParticipants with normal cognition (n = 86) or mild cognitive impairment (n = 53) were selected from the Alzheimer’s Disease Neuroimaging Initiative. MBI scores were derived from Neuropsychiatric Inventory items. Plasma Aβ42/Aβ40 ratios were assayed using mass spectrometry. Linear regressions were fitted to assess the association between MBI total score as well as MBI domain scores with plasma Aβ42/Aβ40.ResultsLower plasma Aβ42/Aβ40 was associated with higher MBI total score (p = 0.04) and greater affective dysregulation (p = 0.04), but not with impaired drive/motivation (p = 0.095) or impulse dyscontrol (p = 0.29) MBI domains.ConclusionIn persons with normal cognition or mild cognitive impairment, MBI was associated with low plasma Aβ42/Aβ40. Incorporating MBI into case detection can help capture preclinical and prodromal Alzheimer’s disease.

scholarly journals Plasma β-Amyloid in Mild Behavioural Impairment – Neuropsychiatric Symptoms on the Alzheimer’s Continuum

2021 ◽  
pp. 089198872110160
Author(s):  
Ruxin Miao ◽  
Hung-Yu Chen ◽  
Sascha Gill ◽  
James Naude ◽  
Eric E. Smith ◽  
...  
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Cognitive Impairment ◽  
Mild Cognitive Impairment ◽  
Neuropsychiatric Symptoms ◽  
Affective Dysregulation ◽  
Prodromal Alzheimer’S Disease ◽  
Amyloid Aβ ◽  
Β Amyloid ◽  
Normal Cognition

Introduction: Simple markers are required to recognize older adults at higher risk for neurodegenerative disease. Mild behavioural impairment (MBI) and plasma β-amyloid (Aβ) have been independently implicated in the development of incident cognitive decline and dementia. Here we studied the associations between MBI and plasma Aβ42/Aβ40. Methods: Participants with normal cognition (n = 86) or mild cognitive impairment (n = 53) were selected from the Alzheimer’s Disease Neuroimaging Initiative. MBI scores were derived from Neuropsychiatric Inventory items. Plasma Aβ42/Aβ40 ratios were assayed using mass spectrometry. Linear regressions were fitted to assess the association between MBI total score as well as MBI domain scores with plasma Aβ42/Aβ40. Results: Lower plasma Aβ42/Aβ40 was associated with higher MBI total score ( p = 0.04) and greater affective dysregulation ( p = 0.04), but not with impaired drive/motivation ( p = 0.095) or impulse dyscontrol ( p = 0.29) MBI domains. Conclusion: In persons with normal cognition or mild cognitive impairment, MBI was associated with low plasma Aβ42/Aβ40. Incorporating MBI into case detection may help capture preclinical and prodromal Alzheimer’s disease.

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

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.

A Biomarker Combining Imaging and Neuropsychological Assessment for Tracking Early Alzheimer's Disease in Clinical Trials

2018 ◽  
Vol 15 (5) ◽  
pp. 429-442 ◽  
Author(s):  
Nishant Verma ◽  
S. Natasha Beretvas ◽  
Belen Pascual ◽  
Joseph C. Masdeu ◽  
Mia K. Markey ◽  
...  
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Clinical Trials ◽  
Cognitive Impairment ◽  
Latent Variable ◽  
Brain Regions ◽  
Disease Assessment ◽  
Latent Variable Analysis ◽  
The Relationship ◽  
Selection Of

Background: Combining optimized cognitive (Alzheimer's Disease Assessment Scale- Cognitive subscale, ADAS-Cog) and atrophy markers of Alzheimer's disease for tracking progression in clinical trials may provide greater sensitivity than currently used methods, which have yielded negative results in multiple recent trials. Furthermore, it is critical to clarify the relationship among the subcomponents yielded by cognitive and imaging testing, to address the symptomatic and anatomical variability of Alzheimer's disease. Method: Using latent variable analysis, we thoroughly investigated the relationship between cognitive impairment, as assessed on the ADAS-Cog, and cerebral atrophy. A biomarker was developed for Alzheimer's clinical trials that combines cognitive and atrophy markers. Results: Atrophy within specific brain regions was found to be closely related with impairment in cognitive domains of memory, language, and praxis. The proposed biomarker showed significantly better sensitivity in tracking progression of cognitive impairment than the ADAS-Cog in simulated trials and a real world problem. The biomarker also improved the selection of MCI patients (78.8±4.9% specificity at 80% sensitivity) that will evolve to Alzheimer's disease for clinical trials. Conclusion: The proposed biomarker provides a boost to the efficacy of clinical trials focused in the mild cognitive impairment (MCI) stage by significantly improving the sensitivity to detect treatment effects and improving the selection of MCI patients that will evolve to Alzheimer’s disease.

scholarly journals Effects of Anosognosia on Perceived Stress and Cortisol Levels in Alzheimer’s Disease

2012 ◽  
Vol 2012 ◽  
pp. 1-7 ◽  
Author(s):  
Genevieve Arsenault-Lapierre ◽  
Victor Whitehead ◽  
Sonia Lupien ◽  
Howard Chertkow
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Cognitive Impairment ◽  
Mild Cognitive Impairment ◽  
Perceived Stress ◽  
Cognitive Deficits ◽  
Salivary Cortisol ◽  
Newly Diagnosed ◽  
Stress Scale ◽  
Cortisol Levels

Anosognosia, or unawareness of one’s own cognitive deficits, may cause issues when measuring perceived stress and cortisol levels in Alzheimer’s disease (AD) and Mild Cognitive Impairment (MCI). The goal of this study was to examine the effects of anosognosia on perceived stress and salivary cortisol levels in normal elderly (NE) adults, MCI individuals, newly diagnosed AD patients, and long-lasting AD patients, suspected to show more anosognosia. An anosognosia index for perceived stress was computed by subtracting the score on the Perceived Stress Scale measured in the participants and their relative. Cortisol levels were measured four times a day over two nonconsecutive days. Greater anosognosia for dementia correlated with greater anosognosia for perceived stress in the group as a whole. However, no correlation between cortisol levels and either anosognosia for dementia or perceived stress was observed. Our results suggest that measuring perceived stress in AD patients may be influenced by anosognosia.

scholarly journals Macroautophagy—a novel β-amyloid peptide-generating pathway activated in Alzheimer's disease

2005 ◽  
Vol 171 (1) ◽  
pp. 87-98 ◽  
Author(s):  
W. Haung Yu ◽  
Ana Maria Cuervo ◽  
Asok Kumar ◽  
Corrinne M. Peterhoff ◽  
Stephen D. Schmidt ◽  
...  
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Cell Survival ◽  
Mammalian Target Of Rapamycin ◽  
Amyloid Peptide ◽  
Survival Pathways ◽  
Secretase Activity ◽  
Amyloid Aβ ◽  
Β Amyloid ◽  
Β Amyloid Peptide

Macroautophagy, which is a lysosomal pathway for the turnover of organelles and long-lived proteins, is a key determinant of cell survival and longevity. In this study, we show that neuronal macroautophagy is induced early in Alzheimer's disease (AD) and before β-amyloid (Aβ) deposits extracellularly in the presenilin (PS) 1/Aβ precursor protein (APP) mouse model of β-amyloidosis. Subsequently, autophagosomes and late autophagic vacuoles (AVs) accumulate markedly in dystrophic dendrites, implying an impaired maturation of AVs to lysosomes. Immunolabeling identifies AVs in the brain as a major reservoir of intracellular Aβ. Purified AVs contain APP and β-cleaved APP and are highly enriched in PS1, nicastrin, and PS-dependent γ-secretase activity. Inducing or inhibiting macroautophagy in neuronal and nonneuronal cells by modulating mammalian target of rapamycin kinase elicits parallel changes in AV proliferation and Aβ production. Our results, therefore, link β-amyloidogenic and cell survival pathways through macroautophagy, which is activated and is abnormal in AD.

scholarly journals The Correlations Between Plasma Fibrinogen With Amyloid-Beta and Tau Levels in Patients With Alzheimer’s Disease

2021 ◽  
Vol 14 ◽  
Author(s):  
Dong-Yu Fan ◽  
Hao-Lun Sun ◽  
Pu-Yang Sun ◽  
Jie-Ming Jian ◽  
Wei-Wei Li ◽  
...  
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Plasma Fibrinogen ◽  
Cognitively Normal ◽  
Amyloid Aβ ◽  
And Gender ◽  
T Tau ◽  
The Relationship ◽  
Phosphorylated Tau 181 ◽  
Normal Controls

Recent studies show that fibrinogen plays a role in the pathogenesis of Alzheimer’s disease (AD), which may be crucial to neurovascular damage and cognitive impairment. However, there are few clinical studies on the relationship between fibrinogen and AD. 59 11C-PiB-PET diagnosed AD patients and 76 age- and gender-matched cognitively normal controls were included to analyze the correlation between plasma β-amyloid (Aβ) and tau levels with fibrinogen levels. 35 AD patients and 76 controls with cerebrospinal fluid (CSF) samples were included to further analyze the correlation between CSF Aβ and tau levels with fibrinogen levels. In AD patients, plasma fibrinogen levels were positively correlated with plasma Aβ40 and Aβ42 levels, and negatively correlated with CSF Aβ42 levels. Besides, fibrinogen levels were positively correlated with CSF total tau (t-tau), and phosphorylated tau-181 (p-tau) levels and positively correlated with the indicators of Aβ deposition in the brain, such as t-tau/Aβ42, p-tau/Aβ42 levels. In normal people, fibrinogen levels lack correlation with Aβ and tau levels in plasma and CSF. This study suggests that plasma fibrinogen levels are positively correlated with Aβ levels in the plasma and brain in AD patients. Fibrinogen may be involved in the pathogenesis of AD.

scholarly journals Microglial and Astrocyte priming in the APP/PS1 model of Alzheimer’s Disease: increased vulnerability to acute inflammation and cognitive deficits

2018 ◽  
Author(s):  
Ana Belen Lopez-Rodriguez ◽  
Edel Hennessy ◽  
Carol Murray ◽  
Anouchka Lewis ◽  
Niamh de Barra ◽  
...  
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Cognitive Deficits ◽  
Inflammasome Activation ◽  
Nuclear Localisation ◽  
Amyloid Pathology ◽  
Model Of Alzheimer’S Disease ◽  
Nlrp3 Inflammasome Activation ◽  
Β Amyloid ◽  
Secondary Stimulation

AbstractAlzheimer’s disease (AD) causes devastating cognitive decline and has no disease-modifying therapies. Neuroinflammation is a significant contributor to disease progression but its precise contribution remains unclear. An emerging literature indicates that secondary inflammatory insults including acute trauma and infection alter the trajectory of chronic neurodegenerative diseases and the roles of microglia and astrocytes require elucidation. The current study, using the APP/PS1 mouse model of AD, demonstrates that microglia are primed by β-amyloid pathology to induce exaggerated IL-1β responses to acute stimulation with LPS or IL-1β. Despite disease-associated NLRP3 inflammasome activation, evidenced by ASC speck formation, APP/PS1 microglial cells show neither IL-1β induction nor NFκB p65 nuclear localisation. Upon secondary stimulation with LPS or IL-1β, NFκB-p65 nuclear localisation and exaggerated pro-IL-1 induction occur. Microglial priming was also unmasked by secondary stimulation with systemic LPS leading to significant cognitive impairment in APP/PS1 mice compared to WT LPS-treated mice. Astrocytes have also recently emerged as displaying significant phenotypic heterogeneity. Here, by-passing microglial priming, and acutely challenging mice with intra-hippocampal IL-1β we demonstrate that astrocytes proximal to Aβ-plaques are also primed to produce exaggerated CCL2, CXCL1 and CXCL10 responses. Many astrocytosis-associated genes in APP/PS1 mice share these exaggerated responses to IL-1β, while others are equally induced in both strains. Collectively the data show that the amyloid-laden brain shows multiple vulnerabilities to secondary inflammatory challenge: both microglia and astrocytes are primed to produce exaggerated secondary inflammation and systemic LPS is sufficient to cause cognitive impairments relevant to delirium, selectively in animals with prior amyloid pathology.

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