Optimizing Modifiable and Lifestyle-related Factors in the Prevention of Dementia Disorders with Special Reference to Alzheimer, Parkinson and Autism Diseases

2020 ◽  
Vol 16 (6) ◽  
pp. 900-911
Author(s):  
Umesh C. Gupta ◽  
Subhas C. Gupta
Keyword(s):  
Physical Activity ◽  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Environmental Pollutants ◽  
Memory Loss ◽  
Tau Proteins ◽  
Body Parts ◽  
Related Factors ◽  
Age Related ◽  
Major Factors

Dementia is a syndrome and an umbrella term that encompasses Alzheimer, Parkinson and autism diseases. These diseases are by far the most common cause of dementia; therefore this investigation will chiefly include these disorders, with a limited discussion of few other disorders related to dementia. Alzheimer’s disease (AD) is characterized by the accumulation of cerebral β-amyloid plaques, tau proteins and memory loss; Parkinson by the deterioration of brain cells which regulate the movement of body parts and produce dopamine; and autism by abnormalities of social disorder and difficulty in communicating and forming relationships. Alzheimer’s disease and cognitive impairment in dementia are age-related and manageable only with early diagnosis and prevention. Data based on several decades of research has shown that the major factors responsible for the induction of inflammation in dementia and many chronic diseases are infections, obesity, alcohol, radiation, environmental pollutants, improper nutrition, lack of physical activity, depression, anxiety, genetic factors, and sleep deprivation. There are some studied preventive measures for dementia including continued physical activity and consuming predominantly a plant-based Mediterranean diet comprising olive oil and foods containing flavonoids and other phytochemicals having strong antioxidant and anti-inflammatory properties and along with management of chronic conditions.

Putative Factors Interfering Cell Cycle Re-Entry in Alzheimer’s Disease: An Omics Study with Differential Expression Meta-Analytics and Co-Expression Profiling

2021 ◽  
pp. 1-26
Author(s):  
Sze Chung Yuen ◽  
Simon Ming-Yuen Lee ◽  
Siu-wai Leung
Keyword(s):  
Alzheimer’S Disease ◽  
Cell Cycle ◽  
Alzheimer's Disease ◽  
Expression Analysis ◽  
Protein Interaction ◽  
Meta Analysis ◽  
Differentially Expressed ◽  
Tau Proteins ◽  
Related Factors ◽  
Protein Protein Interaction

Background: Neuronal cell cycle re-entry (CCR) is a mechanism, along with amyloid-β (Aβ) oligomers and hyperphosphorylated tau proteins, contributing to toxicity in Alzheimer’s disease (AD). Objective: This study aimed to examine the putative factors in CCR based on evidence corroboration by combining meta-analysis and co-expression analysis of omic data. Methods: The differentially expressed genes (DEGs) and CCR-related modules were obtained through the differential analysis and co-expression of transcriptomic data, respectively. Differentially expressed microRNAs (DEmiRNAs) were extracted from the differential miRNA expression studies. The dysregulations of DEGs and DEmiRNAs as binary outcomes were independently analyzed by meta-analysis based on a random-effects model. The CCR-related modules were mapped to human protein-protein interaction databases to construct a network. The importance score of each node within the network was determined by the PageRank algorithm, and nodes that fit the pre-defined criteria were treated as putative CCR-related factors. Results: The meta-analysis identified 18,261 DEGs and 36 DEmiRNAs, including genes in the ubiquitination proteasome system, mitochondrial homeostasis, and CCR, and miRNAs associated with AD pathologies. The co-expression analysis identified 156 CCR-related modules to construct a protein-protein interaction network. Five genes, UBC, ESR1, EGFR, CUL3, and KRAS, were selected as putative CCR-related factors. Their functions suggested that the combined effects of cellular dyshomeostasis and receptors mediating Aβ toxicity from impaired ubiquitination proteasome system are involved in CCR. Conclusion: This study identified five genes as putative factors and revealed the significance of cellular dyshomeostasis in the CCR of AD.

Clinical course of Alzheimer’s disease

2011 ◽  
Author(s):  
Alberto Lleo ◽  
Rafael Blesa
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Daily Living ◽  
Clinical Course ◽  
Neurodegenerative Disorder ◽  
Memory Loss ◽  
Remote Memory ◽  
Initial Symptom ◽  
Delayed Recall ◽  
Age Related

• Alzheimer’s disease is an age-related neurodegenerative disorder, with onset usually in late life, characterized by cognitive impairment, a variety of behavioural symptoms, and restrictions in the activities of daily living• The initial symptom is episodic memory loss, in particular in delayed recall of visual and/or verbal material. Immediate and remote memory is usually preserved in early stages...

scholarly journals Neuron loss associated with age but not Alzheimer's disease pathology in the chimpanzee brain

2020 ◽  
Vol 375 (1811) ◽  
pp. 20190619 ◽  
Author(s):  
Melissa K. Edler ◽  
Emily L. Munger ◽  
Richard S. Meindl ◽  
William D. Hopkins ◽  
John J. Ely ◽  
...  
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Neurofibrillary Tangle ◽  
Cell Loss ◽  
Tau Proteins ◽  
Middle Temporal Gyrus ◽  
Neuron Death ◽  
Neuron Loss ◽  
Neuron Density ◽  
Age Related

In the absence of disease, ageing in the human brain is accompanied by mild cognitive dysfunction, gradual volumetric atrophy, a lack of significant cell loss, moderate neuroinflammation, and an increase in the amyloid beta (A β ) and tau proteins. Conversely, pathologic age-related conditions, particularly Alzheimer's disease (AD), result in extensive neocortical and hippocampal atrophy, neuron death, substantial A β plaque and tau-associated neurofibrillary tangle pathologies, glial activation and severe cognitive decline. Humans are considered uniquely susceptible to neurodegenerative disorders, although recent studies have revealed A β and tau pathology in non-human primate brains. Here, we investigate the effect of age and AD-like pathology on cell density in a large sample of postmortem chimpanzee brains ( n = 28, ages 12–62 years). Using a stereologic, unbiased design, we quantified neuron density, glia density and glia:neuron ratio in the dorsolateral prefrontal cortex, middle temporal gyrus, and CA1 and CA3 hippocampal subfields. Ageing was associated with decreased CA1 and CA3 neuron densities, while AD pathologies were not correlated with changes in neuron or glia densities. Differing from cerebral ageing and AD in humans, these data indicate that chimpanzees exhibit regional neuron loss with ageing but appear protected from the severe cell death found in AD. This article is part of the theme issue ‘Evolution of the primate ageing process’.

Age-Associated Memory Loss: Initial Neuropsychological and Cerebral Metabolic Findings of a Longitudinal Study

1994 ◽  
Vol 6 (1) ◽  
pp. 23-44 ◽  
Author(s):  
Gary W. Small ◽  
Anna Okonek ◽  
Mark A. Mandelkern ◽  
Asenath La Rue ◽  
Linda Chang ◽  
...  
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Longitudinal Study ◽  
Cognitive Abilities ◽  
Mood State ◽  
Familial Risk ◽  
Memory Loss ◽  
Subjective Memory ◽  
Age Related ◽  
Positron Emission

To determine the relationships between clinical and brain function in persons with a familial risk for Alzheimer's disease, the authors assessed subjective and objective cognitive abilities, mood state, and cerebral glucose metabolism (using positron emission tomography) in 43 persons with age-associated memory impairment, with and without first-degree relatives with a clinical diagnosis of Alzheimer's disease. Subjective complaints of memory loss, mood state ratings, and objective memory measures were similar in persons with a family history of Alzheimer's disease (n = 29) compared to those without such a history (n = 14). Metabolic ratios in the frontal regions correlated with a decrease in a specific type of subjective memory complaint (mnemonics usage; p < .001) and some mood state ratings. These results indicate that parietal and temporal hypometabolism is not evident in persons with mild age-related memory complaints, even when such subjects have a familial risk for Alzheimer's disease. Moreover, self-reports of mnemonics usage may be sensitive indicators of decreased frontal lobe function. Longitudinal study will determine whether such clinical and metabolic measures will predict eventual disease progression.

scholarly journals Alzheimer’s disease: many failed trials, so where do we go from here?

2020 ◽  
Vol 68 (6) ◽  
pp. 1135-1140 ◽  
Author(s):  
Allison Bethanne Reiss ◽  
Amy D Glass ◽  
Thomas Wisniewski ◽  
Benjamin Wolozin ◽  
Irving H Gomolin ◽  
...  
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Current Knowledge ◽  
Memory Loss ◽  
Treatment Strategies ◽  
Amyloid Β ◽  
Tau Proteins ◽  
Brain Disorder ◽  
The Central Nervous System ◽  
Progressive Cognitive Impairment

Alzheimer’s disease (AD) is a neurodegenerative brain disorder associated with relentlessly progressive cognitive impairment and memory loss. AD pathology proceeds for decades before cognitive deficits become clinically apparent, opening a window for preventative therapy. Imbalance of clearance and buildup of amyloid β and phosphorylated tau proteins in the central nervous system is believed to contribute to AD pathogenesis. However, multiple clinical trials of treatments aimed at averting accumulation of these proteins have yielded little success, and there is still no disease-modifying intervention. Here, we discuss current knowledge of AD pathology and treatment with an emphasis on emerging biomarkers and treatment strategies.

scholarly journals Potential Roles of Sestrin2 in Alzheimer’s Disease: Antioxidation, Autophagy Promotion, and Beyond

Biomedicines ◽  
2021 ◽  
Vol 9 (10) ◽  
pp. 1308
Author(s):  
Shang-Der Chen ◽  
Jenq-Lin Yang ◽  
Yi-Heng Hsieh ◽  
Tsu-Kung Lin ◽  
Yi-Chun Lin ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Neurodegenerative Diseases ◽  
Memory Loss ◽  
Oxygen Species ◽  
Mechanistic Target Of Rapamycin ◽  
Cell Cycle Reentry ◽  
Age Related ◽  
Reduce Activity

Alzheimer's disease (AD) is the most common age-related neurodegenerative disease. It presents with progressive memory loss, worsens cognitive functions to the point of disability, and causes heavy socioeconomic burdens to patients, their families, and society as a whole. The underlying pathogenic mechanisms of AD are complex and may involve excitotoxicity, excessive generation of reactive oxygen species (ROS), aberrant cell cycle reentry, impaired mitochondrial function, and DNA damage. Up to now, there is no effective treatment available for AD, and it is therefore urgent to develop an effective therapeutic regimen for this devastating disease. Sestrin2, belonging to the sestrin family, can counteract oxidative stress, reduce activity of the mammalian/mechanistic target of rapamycin (mTOR), and improve cell survival. It may therefore play a crucial role in neurodegenerative diseases like AD. However, only limited studies of sestrin2 and AD have been conducted up to now. In this article, we discuss current experimental evidence to demonstrate the potential roles of sestrin2 in treating neurodegenerative diseases, focusing specifically on AD. Strategies for augmenting sestrin2 expression may strengthen neurons, adapting them to stressful conditions through counteracting oxidative stress, and may also adjust the autophagy process, these two effects together conferring neuronal resistance in cases of AD.

Exposure to Traffic-Generated Pollutants Exacerbates the Expression of Factors Associated with the Pathophysiology of Alzheimer’s Disease in Aged C57BL/6 Wild-Type Mice

2021 ◽  
Author(s):  
Tyler D. Armstrong ◽  
Usa Suwannasual ◽  
Conner L. Kennedy ◽  
Akshaykumar Thasma ◽  
Leah J. Schneider ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Environmental Pollutants ◽  
Amyloid Β ◽  
At1 Receptor ◽  
Aryl Hydrocarbon ◽  
Ca1 Region ◽  
Age Related ◽  
Regulatory Standards

Background: Multiple studies report a strong correlation between traffic-generated air pollution-exposure and detrimental outcomes in the central nervous system (CNS), including Alzheimer’s disease (AD). Incidence of AD is rapidly increasing and, worldwide, many live in regions where pollutants exceed regulatory standards. Thus, it is imperative to identify environmental pollutants that contribute to AD, and the mechanisms involved. Objective: We investigated the effects of mixed gasoline and diesel engine emissions (MVE) on the expression of factors involved in progression of AD in the hippocampus and cerebrum in a young versus aged mouse model. Methods: Young (2 months old) and aged (18 months old) male C57BL/6 mice were exposed to either MVE (300 μg/m3 PM) or filtered air (FA) for 6 h/d, 7 d/wk, for 50 d. Immunofluorescence and RT-qPCR were used to quantify oxidative stress (8-OHdG) and expression of amyloid-β protein precursor (AβPP), β secretase (BACE1), amyloid-β (Aβ), aryl hydrocarbon receptor (AhR), cytochrome P450 (CYP) 1B1, angiotensin-converting enzyme (ACE1), and angiotensin II type 1 (AT1) receptor in the cerebrum and hippocampus, in addition to cerebral microvascular tight junction (TJ) protein expression. Results: We observed age-related increases in oxidative stress, AhR, CYP1B1, Aβ, BACE1, and AT1 receptor in the CA1 region of the hippocampus, and elevation of cerebral AβPP, AhR, and CYP1B1 mRNA, associated with decreased cerebral microvascular TJ protein claudin-5. MVE-exposure resulted in further promotion of oxidative stress, and significant increases in AhR, CYP1B1, BACE1, ACE1, and Aβ, compared to the young and aged FA-exposed mice. Conclusion: Such findings suggest that MVE-exposure exacerbates the expression of factors in the CNS associated with AD pathogenesis in aged populations.

scholarly journals Effects of Reactive Oxygen and Nitrogen Species on TrkA Expression and Signalling: Implications for proNGF in Aging and Alzheimer’s Disease

Cells ◽  
2021 ◽  
Vol 10 (8) ◽  
pp. 1983
Author(s):  
Erika Kropf ◽  
Margaret Fahnestock
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Cognitive Function ◽  
Basal Forebrain ◽  
Memory Loss ◽  
Reactive Oxygen ◽  
Neurotrophin Receptor ◽  
Nitrogen Species ◽  
Age Related ◽  
The Brain

Nerve growth factor (NGF) and its precursor form, proNGF, are critical for neuronal survival and cognitive function. In the brain, proNGF is the only detectable form of NGF. Dysregulation of proNGF in the brain is implicated in age-related memory loss and Alzheimer’s disease (AD). AD is characterized by early and progressive degeneration of the basal forebrain, an area critical for learning, memory, and attention. Learning and memory deficits in AD are associated with loss of proNGF survival signalling and impaired retrograde transport of proNGF to the basal forebrain. ProNGF transport and signalling may be impaired by the increased reactive oxygen and nitrogen species (ROS/RNS) observed in the aged and AD brain. The current literature suggests that ROS/RNS nitrate proNGF and reduce the expression of the proNGF receptor tropomyosin-related kinase A (TrkA), disrupting its downstream survival signalling. ROS/RNS-induced reductions in TrkA expression reduce cell viability, as proNGF loses its neurotrophic function in the absence of TrkA and instead generates apoptotic signalling via the pan-neurotrophin receptor p75NTR. ROS/RNS also interfere with kinesin and dynein motor functions, causing transport deficits. ROS/RNS-induced deficits in microtubule motor function and TrkA expression and signalling may contribute to the vulnerability of the basal forebrain in AD. Antioxidant treatments may be beneficial in restoring proNGF signalling and axonal transport and reducing basal forebrain neurodegeneration and related deficits in cognitive function.

Exposure to Traffic-Generated Pollutants Exacerbates the Expression of Factors Associated with the Pathophysiology of Alzheimer’s Disease in Aged C57BL/6 Wild-Type Mice

2020 ◽  
Vol 78 (4) ◽  
pp. 1453-1471
Author(s):  
Tyler D. Armstrong ◽  
Usa Suwannasual ◽  
Conner L. Kennedy ◽  
Akshaykumar Thasma ◽  
Leah J. Schneider ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Environmental Pollutants ◽  
Amyloid Β ◽  
At1 Receptor ◽  
Aged Mouse ◽  
Amyloid Β Protein ◽  
Ca1 Region ◽  
Age Related

Background: Multiple studies report a strong correlation between traffic-generated air pollution-exposure and detrimental outcomes in the central nervous system (CNS), including Alzheimer’s disease (AD). Incidence of AD is rapidly increasing and, worldwide, many live in regions where pollutants exceed regulatory standards. Thus, it is imperative to identify environmental pollutants that contribute to AD, and the mechanisms involved. Objective: We investigated the effects of mixed gasoline and diesel engine emissions (MVE) on the expression of factors involved in progression of AD in the hippocampus and cerebrum in a young versus aged mouse model. Methods: Young (2 months old) and aged (18 months old) male C57BL/6 mice were exposed to either MVE (300μg/m3 PM) or filtered air (FA) for 6 h/d, 7 d/wk, for 50 d. Immunofluorescence and RT-qPCR were used to quantify oxidative stress (8-OHdG) and expression of amyloid-β protein precursor (AβPP), β secretase (BACE1), amyloid-β (Aβ), aryl hydrocarbon receptor (AhR), cytochrome P450 (CYP) 1B1, angiotensin-converting enzyme (ACE1), and angiotensin II type 1 (AT1) receptor in the cerebrum and hippocampus, in addition to cerebral microvascular tight junction (TJ) protein expression. Results: We observed age-related increases in oxidative stress, AhR, CYP1B1, Aβ, BACE1, and AT1 receptor in the CA1 region of the hippocampus, and elevation of cerebral AβPP, AhR, and CYP1B1 mRNA, associated with decreased cerebral microvascular TJ protein claudin-5. MVE-exposure resulted in further promotion of oxidative stress, and significant increases in AhR, CYP1B1, BACE1, ACE1, and Aβ, compared to the young and aged FA-exposed mice. Conclusion: Such findings suggest that MVE-exposure exacerbates the expression of factors in the CNS associated with AD pathogenesis in aged populations.

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