Brain Imaging in Alzheimer Disease

Cold Spring Harbor Perspectives in Medicine, Год журнала: 2012, Номер 2(4), С. a006213 - a006213

Опубликована: Янв. 31, 2012

Imaging has played a variety of roles in the study Alzheimer disease (AD) over past four decades. Initially, computed tomography (CT) and then magnetic resonance imaging (MRI) were used diagnostically to rule out other causes dementia. More recently, modalities including structural functional MRI positron emission (PET) studies cerebral metabolism with fluoro-deoxy-d-glucose (FDG) amyloid tracers such as Pittsburgh Compound-B (PiB) have shown characteristic changes brains patients AD, prodromal even presymptomatic states that can help rule-in AD pathophysiological process. No one modality serve all purposes each unique strengths weaknesses. These their particular utilities are discussed this article. The challenge for future will be combine biomarkers most efficiently facilitate diagnosis, staging, and, importantly, development effective disease-modifying therapies.

Язык: Английский

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Long-chain omega-3 fatty acids and the brain: a review of the independent and shared effects of EPA, DPA and DHA

Frontiers in Aging Neuroscience, Год журнала: 2015, Номер 7

Опубликована: Апрель 21, 2015

Omega-3 polyunsaturated fatty acids (PUFAs) exhibit neuroprotective properties and represent a potential treatment for variety of neurodegenerative neurological disorders. However, traditionally there has been lack discrimination between the different omega-3 PUFAs effects have broadly accredited to series as whole. Evidence unique eicosapentaenoic acid (EPA), docosahexaenoic (DHA) more recently docosapentaenoic (DPA) is growing. For example, beneficial in mood disorders consistently reported clinical trials using EPA; whereas, with conditions such Alzheimer's disease, focus on DHA. DHA quantitatively most important PUFA brain, consequently studied, whereas availability high purity DPA preparations extremely limited until recently, limiting research into its effects. now growing body evidence indicating both independent shared EPA, The purpose this review highlight how detailed understanding these essential improving their therapeutic potential. begins an overview biochemistry metabolism, particular central nervous system, where indispensable roles neuronal membranes levels preserved by multiple mechanisms. This followed enzyme-derived anti-inflammatory mediators produced from Lastly, relative protective normal brain aging common are discussed. With greater individual health repair it hoped that appropriate dietary recommendations can be established interventions targeted refined.

Язык: Английский

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The preclinical phase of the pathological process underlying sporadic Alzheimer’s disease

Brain, Год журнала: 2015, Номер 138(10), С. 2814 - 2833

Опубликована: Авг. 17, 2015

Abnormal tau lesions (non-argyrophilic pretangle material, argyrophilic neuropil threads, neurofibrillary tangles) in select types of neurons are crucial for the pathogenesis sporadic Alzheimer's disease. Ongoing formation these persists into end-stage disease and is not subject to remission. The early phase a focus increasing interest because only abnormal forms microtubule-associated protein involved at that point and, contrast late-stage when amyloid-β deposition present, this temporally closer prevailing conditions induce pathological process underlying Extracellular aggregated may be produced under by nerve cells contain tau. One potential trigger hyperphosphorylation conformational change presence non-endogenous pathogen. Subsequently, predictable regional distribution pattern develops phylogenetically late-appearing ontogenetically late-maturing connected via their axons. It hoped hypotheses drawn from considerations, as well recent dissemination models, studies variant conformers, imaging will encourage development new preventative disease-modifying strategies.

Язык: Английский

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Neuron loss in the 5XFAD mouse model of Alzheimer’s disease correlates with intraneuronal Aβ42 accumulation and Caspase-3 activation

Molecular Neurodegeneration, Год журнала: 2013, Номер 8(1), С. 2 - 2

Опубликована: Янв. 1, 2013

Although the mechanism of neuron loss in Alzheimer’s disease (AD) is enigmatic, it associated with cerebral accumulation Aβ42. The 5XFAD mouse model amyloid deposition expresses five familial AD (FAD) mutations that are additive driving Aβ42 overproduction. mice exhibit intraneuronal at 1.5 months, 2 and memory deficits by 4 months age. Here, we demonstrate unbiased stereology statistically significant occurs 9 age mice. We validated two Aβ42-selective antibodies immunostaining 5XFAD; BACE1−/− bigenic brain sections then used these to show develop same regions where observed brain. In neuronal soma, accumulates puncta co-label for Transferrin receptor LAMP-1, indicating endosomal lysosomal localization, respectively. addition, young brains, activated Caspase-3 soma proximal dendrites Aβ42-labeled neurons. older found Caspase-3-positive punctate accumulations co-localize marker class III β-tubulin, suggesting apoptosis. Together, our results indicate a temporal sequence accumulation, activation, implies potential apoptotic death mouse.

Язык: Английский

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Synaptopathies: synaptic dysfunction in neurological disorders – A review from students to students

Journal of Neurochemistry, Год журнала: 2016, Номер 138(6), С. 785 - 805

Опубликована: Июнь 23, 2016

Abstract Synapses are essential components of neurons and allow information to travel coordinately throughout the nervous system adjust behavior environmental stimuli control body functions, memories, emotions. Thus, optimal synaptic communication is required for proper brain physiology, slight perturbations synapse function can lead disorders. In fact, increasing evidence has demonstrated relevance dysfunction as a major determinant many neurological diseases. This notion led concept synaptopathies diseases with defects shared pathogenic features. this review, which was initiated at 13th International Society Neurochemistry Advanced School, we discuss basic concepts structure function, provide critical view how aberrant physiology may contribute neurodevelopmental disorders (autism, Down syndrome, startle disease, epilepsy) well neurodegenerative (Alzheimer Parkinson disease). We finally appropriateness potential implications gathering under single term. Understanding common causes intrinsic differences in disease‐associated could offer novel clues toward synapse‐based therapeutic intervention neuropsychiatric image Review, ( ISN ) (Alzheimer's Parkinson's diseases), gathered together term synaptopathies. Read Editorial Highlight article on page 783 .

Язык: Английский

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Insulin resistance as a key link for the increased risk of cognitive impairment in the metabolic syndrome

Experimental & Molecular Medicine, Год журнала: 2015, Номер 47(3), С. e149 - e149

Опубликована: Март 13, 2015

Metabolic syndrome (MetS) is a cluster of cardiovascular risk factors that includes obesity, diabetes, and dyslipidemia. Accumulating evidence implies MetS contributes to the development progression Alzheimer's disease (AD); however, connecting this association have not been determined. Insulin resistance (IR) at core likely represent key link between AD. In central nervous system, insulin plays roles in learning memory, AD patients exhibit impaired signaling similar observed MetS. As we face an alarming increase obesity T2D all age groups, understanding relationship vital for identification potential therapeutic targets. Recently, several diabetes therapies enhance are being tested benefit dementia. review, will discuss as factor AD, focusing on IR recent progress future directions insulin-based therapies. Mounting evidences suggest strong associated with metabolic syndrome. The hormone best known managing blood sugar levels but it also regulates numerous brain functions. review by Bhumsoo Kim Eva Feldman University Michigan USA suggets abnormalities intimately connected neurodegeneration dementia seen disease. Individuals type 2 or exhibiting abnormal lipid precede considerably greater Disrupted appears actively promote accumulation toxic protein clumps primary hallmarks neurological disorder. authors interventions target pathways slow

Язык: Английский

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Wnt signaling in the nervous system and in Alzheimer's disease

Journal of Molecular Cell Biology, Год журнала: 2014, Номер 6(1), С. 64 - 74

Опубликована: Фев. 1, 2014

Wnts comprise a large family of proteins that have shown to be part signaling cascade regulates several aspects development including organogenesis, midbrain as well stem cell proliferation. Wnt pathway plays different roles in the neuronal circuits and also adult brain, where it synaptic transmission plasticity. It has been implicated various diseases cancer neurodegenerative diseases, reflecting its relevance fundamental biological processes. This review summarizes progress about function mature nervous system with focus on Alzheimer's disease (AD). We discuss prospects modulating canonical non-canonical strategy for neuroprotection. will include potential to: (i) act potent regulators hippocampal synapses impact learning memory; (ii) regulate neurogenesis; finally (iii) control AD pathogenesis.

Язык: Английский

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Potential neuroprotective properties of epigallocatechin-3-gallate (EGCG)

Nutrition Journal, Год журнала: 2015, Номер 15(1)

Опубликована: Дек. 1, 2015

Neurodegenerative diseases such as Alzheimer’s disease (AD) and Parkinson’s (PD) enforce an overwhelming social economic burden on society. They are primarily characterized through the accumulation of modified proteins, which further trigger biological responses inflammation, oxidative stress, excitotoxicity modulation signalling pathways. In a hope for cure, these have been studied extensively over last decade to successfully develop symptom-oriented therapies. However, so far no definite cure has found. Therefore, there is need identify class drug capable reversing neural damage preventing death. This review therefore assesses reliability neuroprotective benefits epigallocatechin-gallate (EGCG) by shedding light their biological, pharmacological, antioxidant metal chelation properties, with emphasis ability invoke range cellular mechanisms in brain. It also discusses possible use nanotechnology enhance EGCG.

Язык: Английский

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PI3-kinase/Akt/mTOR signaling: Impaired on/off switches in aging, cognitive decline and Alzheimer's disease

Experimental Gerontology, Год журнала: 2013, Номер 48(7), С. 647 - 653

Опубликована: Март 5, 2013

Язык: Английский

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Beneficial Effects of Green Tea Catechins on Neurodegenerative Diseases

Molecules, Год журнала: 2018, Номер 23(6), С. 1297 - 1297

Опубликована: Май 29, 2018

Tea is one of the most consumed beverages in world. Green tea, black and oolong tea are made from same plant Camellia sinensis (L.) O. Kuntze. Among them, green has been extensively studied for beneficial effects on diseases including cancer, obesity, diabetes, inflammatory neurodegenerative diseases. Several human observational intervention studies have found consumption impairment, such as cognitive dysfunction memory loss. These supported basis tea’s preventive Parkinson’s disease, but few revealed Alzheimer’s disease. In contrast, several not reported these favorable with regard to tea. This discrepancy may be due incomplete adjustment confounding factors, method quantifying consumption, beverage temperature, cigarette smoking, alcohol differences genetic environmental race, sex, age, lifestyle. Thus, more rigorous required understand neuroprotective effect A number laboratory experiments demonstrated benefits catechins (GTCs), epigallocatechin gallate (EGCG), proposed action mechanisms. The targets GTCs include abnormal accumulation fibrous proteins, Aβ α-synuclein, inflammation, elevated expression pro-apoptotic oxidative stress, which associated neuronal cell death cerebral cortex. Computational molecular docking analysis how EGCG can prevent proteins. findings suggest that potential used prevention treatment could useful development new drugs.

Язык: Английский

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