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.

scholarly journals Probable Causes of Alzheimer’s Disease

Sci ◽  
2021 ◽  
Vol 3 (1) ◽  
pp. 16
Author(s):  
James David Adams
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Lactic Acid ◽  
Blood Brain Barrier ◽  
Transient Receptor Potential ◽  
Brain Barrier ◽  
Folate Intake ◽  
Blood Brain ◽  
Age Related ◽  
The Brain

A three-part mechanism is proposed for the induction of Alzheimer’s disease: (1) decreased blood lactic acid; (2) increased blood ceramide and adipokines; (3) decreased blood folic acid. The age-related nature of these mechanisms comes from age-associated decreased muscle mass, increased visceral fat and changes in diet. This mechanism also explains why many people do not develop Alzheimer’s disease. Simple changes in lifestyle and diet can prevent Alzheimer’s disease. Alzheimer’s disease is caused by a cascade of events that culminates in damage to the blood–brain barrier and damage to neurons. The blood–brain barrier keeps toxic molecules out of the brain and retains essential molecules in the brain. Lactic acid is a nutrient to the brain and is produced by exercise. Damage to endothelial cells and pericytes by inadequate lactic acid leads to blood–brain barrier damage and brain damage. Inadequate folate intake and oxidative stress induced by activation of transient receptor potential cation channels and endothelial nitric oxide synthase damage the blood–brain barrier. NAD depletion due to inadequate intake of nicotinamide and alterations in the kynurenine pathway damages neurons. Changes in microRNA levels may be the terminal events that cause neuronal death leading to Alzheimer’s disease. A new mechanism of Alzheimer’s disease induction is presented involving lactic acid, ceramide, IL-1β, tumor necrosis factor α, folate, nicotinamide, kynurenine metabolites and microRNA.

scholarly journals Basal Forebrain Cholinergic Neurons: Linking Down Syndrome and Alzheimer’s Disease

2021 ◽  
Vol 13 ◽  
Author(s):  
Jose L. Martinez ◽  
Matthew D. Zammit ◽  
Nicole R. West ◽  
Bradley T. Christian ◽  
Anita Bhattacharyya
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Down Syndrome ◽  
Basal Forebrain ◽  
Critical Role ◽  
Memory Loss ◽  
Cholinergic Neurons ◽  
Cholinergic Innervation ◽  
Attention And Memory ◽  
Basal Forebrain Cholinergic Neurons

Down syndrome (DS, trisomy 21) is characterized by intellectual impairment at birth and Alzheimer’s disease (AD) pathology in middle age. As individuals with DS age, their cognitive functions decline as they develop AD pathology. The susceptibility to degeneration of a subset of neurons, known as basal forebrain cholinergic neurons (BFCNs), in DS and AD is a critical link between cognitive impairment and neurodegeneration in both disorders. BFCNs are the primary source of cholinergic innervation to the cerebral cortex and hippocampus, as well as the amygdala. They play a critical role in the processing of information related to cognitive function and are directly engaged in regulating circuits of attention and memory throughout the lifespan. Given the importance of BFCNs in attention and memory, it is not surprising that these neurons contribute to dysfunctional neuronal circuitry in DS and are vulnerable in adults with DS and AD, where their degeneration leads to memory loss and disturbance in language. BFCNs are thus a relevant cell target for therapeutics for both DS and AD but, despite some success, efforts in this area have waned. There are gaps in our knowledge of BFCN vulnerability that preclude our ability to effectively design interventions. Here, we review the role of BFCN function and degeneration in AD and DS and identify under-studied aspects of BFCN biology. The current gaps in BFCN relevant imaging studies, therapeutics, and human models limit our insight into the mechanistic vulnerability of BFCNs in individuals with DS and AD.

MR Brain Screening using Optimization Techniques – A survey

2021 ◽  
Vol 17 ◽  
Author(s):  
Chitradevi D ◽  
Prabha S.
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Clinical Symptoms ◽  
Memory Loss ◽  
Amyloid Β ◽  
Cell Loss ◽  
Optimization Techniques ◽  
Amyloid Β Protein ◽  
The Brain ◽  
Brain Tissues

Background: Alzheimer’s disease (AD) is associated with Dementia, and it is also a memory syndrome in the brain. It affects the brain tissues and causes major changes in day-to-day activities. Aging is a major cause of Alzheimer's disease. AD is characterized by two pathological hallmarks as, Amyloid β protein and neurofibrillary tangles of hyperphosphorylated tau protein. The imaging hallmarks for Alzheimer’s disease are namely, swelling, shrinkage of brain tissues due to cell loss, and atrophy in the brain due to protein dissemination. Based on the survey, 60% to 80% of dementia patients belong to Alzheimer’s disease. Introduction: AD is now becoming an increasing and important brain disease. The goal of AD pathology is to cause changes/damage in brain tissues. Alzheimer's disease is thought to begin 20 years or more before symptoms appear, with tiny changes in the brain that are undetectable to the person affected. The changes in a person's brain after a few years are noticeable through symptoms such as language difficulties and memory loss. Neurons in different parts of the brain have detected symptoms such as cognitive impairments and learning disabilities. In this case, neuroimaging tools are necessary to identify the development of pathology which relates to the clinical symptoms. Methods: Several approaches have been tried during the last two decades for brain screening to analyse AD with the process of pre-processing, segmentation and classification. Different individual such as Grey Wolf optimization, Lion Optimization, Ant Lion Optimization and so on. Similarly, hybrid optimization techniques are also attempted to segment the brain sub-regions which helps in identifying the bio-markers to analyse AD. Conclusion: This study discusses a review of neuroimaging technologies for diagnosing Alzheimer's disease, as well as the discovery of hallmarks for the disease and the methodologies for finding hallmarks from brain images to evaluate AD. According to the literature review, most of the techniques predicted higher accuracy (more than 90%), which is beneficial for assessing and screening neurodegenerative illness, particularly Alzheimer's disease.

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 Low-Dose Ionizing Radiation Modulates Microglia Phenotypes in the Models of Alzheimer’s Disease

2020 ◽  
Vol 21 (12) ◽  
pp. 4532 ◽  
Author(s):  
Sujin Kim ◽  
Hyunju Chung ◽  
Han Ngoc Mai ◽  
Yunkwon Nam ◽  
Soo Jung Shin ◽  
...  
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Ionizing Radiation ◽  
Cognitive Deficits ◽  
Low Dose ◽  
Memory Loss ◽  
M2 Polarization ◽  
Phenotype Switching ◽  
5Xfad Mice ◽  
The Brain

Alzheimer’s disease (AD) is the most common type of dementia. AD involves major pathologies such as amyloid-β (Aβ) plaques and neurofibrillary tangles in the brain. During the progression of AD, microglia can be polarized from anti-inflammatory M2 to pro-inflammatory M1 phenotype. The activation of triggering receptor expressed on myeloid cells 2 (TREM2) may result in microglia phenotype switching from M1 to M2, which finally attenuated Aβ deposition and memory loss in AD. Low-dose ionizing radiation (LDIR) is known to ameliorate Aβ pathology and cognitive deficits in AD; however, the therapeutic mechanisms of LDIR against AD-related pathology have been little studied. First, we reconfirm that LDIR (two Gy per fraction for five times)-treated six-month 5XFAD mice exhibited (1) the reduction of Aβ deposition, as reflected by thioflavins S staining, and (2) the improvement of cognitive deficits, as revealed by Morris water maze test, compared to sham-exposed 5XFAD mice. To elucidate the mechanisms of LDIR-induced inhibition of Aβ accumulation and memory loss in AD, we examined whether LDIR regulates the microglial phenotype through the examination of levels of M1 and M2 cytokines in 5XFAD mice. In addition, we investigated the direct effects of LDIR on lipopolysaccharide (LPS)-induced production and secretion of M1/M2 cytokines in the BV-2 microglial cells. In the LPS- and LDIR-treated BV-2 cells, the M2 phenotypic marker CD206 was significantly increased, compared with LPS- and sham-treated BV-2 cells. Finally, the effect of LDIR on M2 polarization was confirmed by detection of increased expression of TREM2 in LPS-induced BV2 cells. These results suggest that LDIR directly induced phenotype switching from M1 to M2 in the brain with AD. Taken together, our results indicated that LDIR modulates LPS- and Aβ-induced neuroinflammation by promoting M2 polarization via TREM2 expression, and has beneficial effects in the AD-related pathology such as Aβ deposition and memory loss.

scholarly journals IL-33 ameliorates Alzheimer’s disease-like pathology and cognitive decline

2016 ◽  
Vol 113 (19) ◽  
pp. E2705-E2713 ◽  
Author(s):  
Amy K. Y. Fu ◽  
Kwok-Wang Hung ◽  
Michael Y. F. Yuen ◽  
Xiaopu Zhou ◽  
Deejay S. Y. Mak ◽  
...  
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Immune Response ◽  
Innate Immune Response ◽  
Memory Loss ◽  
Neuronal Loss ◽  
Innate Immune ◽  
Therapeutic Role ◽  
Potential Therapeutic Role ◽  
The Brain

Alzheimer’s disease (AD) is a devastating condition with no known effective treatment. AD is characterized by memory loss as well as impaired locomotor ability, reasoning, and judgment. Emerging evidence suggests that the innate immune response plays a major role in the pathogenesis of AD. In AD, the accumulation of β-amyloid (Aβ) in the brain perturbs physiological functions of the brain, including synaptic and neuronal dysfunction, microglial activation, and neuronal loss. Serum levels of soluble ST2 (sST2), a decoy receptor for interleukin (IL)-33, increase in patients with mild cognitive impairment, suggesting that impaired IL-33/ST2 signaling may contribute to the pathogenesis of AD. Therefore, we investigated the potential therapeutic role of IL-33 in AD, using transgenic mouse models. Here we report that IL-33 administration reverses synaptic plasticity impairment and memory deficits in APP/PS1 mice. IL-33 administration reduces soluble Aβ levels and amyloid plaque deposition by promoting the recruitment and Aβ phagocytic activity of microglia; this is mediated by ST2/p38 signaling activation. Furthermore, IL-33 injection modulates the innate immune response by polarizing microglia/macrophages toward an antiinflammatory phenotype and reducing the expression of proinflammatory genes, including IL-1β, IL-6, and NLRP3, in the cortices of APP/PS1 mice. Collectively, our results demonstrate a potential therapeutic role for IL-33 in AD.

scholarly journals Osmotin-loaded magnetic nanoparticles with electromagnetic guidance for the treatment of Alzheimer's disease

Nanoscale ◽  
2017 ◽  
Vol 9 (30) ◽  
pp. 10619-10632 ◽  
Author(s):  
Faiz Ul Amin ◽  
Ali Kafash Hoshiar ◽  
Ton Duc Do ◽  
Yeongil Noh ◽  
Shahid Ali Shah ◽  
...  
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Magnetic Nanoparticles ◽  
Neurodegenerative Disease ◽  
Amyloid Beta ◽  
Age Related ◽  
Electromagnetic Guidance ◽  
The Brain

Alzheimer's disease (AD) is the most prevalent age-related neurodegenerative disease, pathologically characterized by the accumulation of aggregated amyloid beta (Aβ) in the brain.

scholarly journals Neuronal expression of STM2 mRNA in human brain is reduced in Alzheimer's disease.

1996 ◽  
Vol 44 (11) ◽  
pp. 1215-1222 ◽  
Author(s):  
P J McMillan ◽  
J B Leverenz ◽  
P Poorkaj ◽  
G D Schellenberg ◽  
D M Dorsa
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Human Brain ◽  
Basal Forebrain ◽  
Cell Types ◽  
Hybridization Histochemistry ◽  
In Situ Hybridization Histochemistry ◽  
A Cell ◽  
The Brain

Mutations in the STM2 gene cause familial Alzheimer's disease (AD) in Volga Germans. To understand the function of this protein and how mutations lead to AD, it is important to determine which cell types in the brain express this gene. In situ hybridization histochemistry indicates that STM2 expression in the human brain is widespread and is primarily neuronal. In addition, STM2 mRNA is expressed in a cell line with neuronal origins. Quantification of the level of expression of the STM2 message in the basal forebrain, frontal cortex, and hippocampus reveals a significant decrease in AD-affected subjects compared to normal age-matched controls. These data suggest that downregulation of neuronal STM2 gene expression may be involved in the progression of AD.

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 Age-Related Association between Apolipoprotein E e4 and Cognitive Function in Japanese Patients with Alzheimer's Disease

2013 ◽  
Vol 3 (1) ◽  
pp. 66-73
Author(s):  
Tomoyuki Nagata ◽  
Shunichiro Shinagawa ◽  
Bolati Kuerban ◽  
Nobuto Shibata ◽  
Tohru Ohnuma ◽  
...  
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Cognitive Function ◽  
Apolipoprotein E ◽  
Japanese Patients ◽  
Age Related ◽  
Related Association
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