Emerging concepts in sporadic cerebral amyloid angiopathy

Brain, Год журнала: 2017, Номер 140(7), С. 1829 - 1850

Опубликована: Фев. 27, 2017

Sporadic cerebral amyloid angiopathy is a common, well-defined small vessel disease and largely untreatable cause of intracerebral haemorrhage contributor to age-related cognitive decline. The term 'cerebral angiopathy' now encompasses not only specific cerebrovascular pathological finding, but also different clinical syndromes (both acute progressive), brain parenchymal lesions seen on neuroimaging set diagnostic criteria—the Boston criteria, which have resulted in increasingly detected during life. Over the past few years, it has become clear that, at pathophysiological level, appears be part protein elimination failure that this dysfunction feed-forward process, potentially leads worsening vascular amyloid-β accumulation, activation injury pathways impaired physiology. From standpoint, characterized by individual focal (microbleeds, cortical superficial siderosis, microinfarcts) large-scale alterations (white matter hyperintensities, structural connectivity, thickness), both subcortical. This review provides an interdisciplinary critical outlook various emerging changing concepts field, illustrating mechanisms associated with pathology neurological dysfunction.

Язык: Английский

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Sex and the development of Alzheimer's disease

Journal of Neuroscience Research, Год журнала: 2016, Номер 95(1-2), С. 671 - 680

Опубликована: Ноя. 7, 2016

Men and women exhibit differences in the development progression of Alzheimer's disease (AD). The factors underlying sex AD are not well understood. This Review emphasizes contributions steroid hormones to relationship between AD. In women, events that decrease lifetime exposure estrogens generally associated with increased risk, whereas estrogen-based hormone therapy administered near time menopause may reduce risk. men, do age-related reduction significantly Rather, normal depletions testosterone plasma brain predict enhanced vulnerability Both androgens exert numerous protective actions adult increase neural functioning resilience as specifically attenuating multiple aspects AD-related neuropathology. Aging diminishes activational effects sex-specific manners, which is hypothesized contribute aging Sex also drive through their organizational during developmental sexual differentiation brain. Specifically, early confer inherent female advanced age. combined steroids yield distinct pathogenesis, a significant variable must be more rigorously considered future research. © 2016 Wiley Periodicals, Inc.

Язык: Английский

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Insulin Resistance and Neurodegeneration: Progress Towards the Development of New Therapeutics for Alzheimer’s Disease

Drugs, Год журнала: 2016, Номер 77(1), С. 47 - 65

Опубликована: Дек. 17, 2016

Язык: Английский

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Vascular Dysfunction in Alzheimer’s Disease: A Prelude to the Pathological Process or a Consequence of It?

Journal of Clinical Medicine, Год журнала: 2019, Номер 8(5), С. 651 - 651

Опубликована: Май 10, 2019

Alzheimer's disease (AD) is the most prevalent form of dementia. Despite decades research following several theoretical and clinical lines, all existing treatments for disorder are purely symptomatic. AD has traditionally been focused on neuronal glial dysfunction. Although there a wealth evidence pointing to significant vascular component in disease, this angle relatively poorly explored. In review, we consider various aspects dysfunction AD, which impact brain metabolism homeostasis clearance β-amyloid other toxic metabolites. This may potentially precede onset hallmark pathophysiological cognitive symptoms disease. Pathological changes vessel haemodynamics, angiogenesis, cell function, coverage, blood-brain barrier permeability immune migration be related amyloid toxicity, oxidative stress apolipoprotein E (APOE) genotype. These deficits turn contribute parenchymal deposition, neurotoxicity, activation metabolic multiple types. A vicious feedback cycle ensues, with progressively worsening pathology through course Thus, better appreciation importance open new avenues therapy.

Язык: Английский

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Questions concerning the role of amyloid-β in the definition, aetiology and diagnosis of Alzheimer’s disease

Acta Neuropathologica, Год журнала: 2018, Номер 136(5), С. 663 - 689

Опубликована: Окт. 22, 2018

The dominant hypothesis of Alzheimer's disease (AD) aetiology, the neuropathological guidelines for diagnosing AD and majority high-profile therapeutic efforts, in both research clinical practice, have been built around one possible causal factor, amyloid-β (Aβ). However, link between Aβ remains unproven. Here, context a detailed assessment historical contemporary studies, we raise critical questions regarding role definition, diagnosis aetiology AD. We illustrate that holistic view available data does not support an unequivocal conclusion has central or unique Instead, suggest alternative views are potentially valid, at this time. propose unbiased way forward field, beyond current Aβ-centric approach, without excluding Aβ, is required to come accurate understanding dementia and, ultimately, effective treatment.

Язык: Английский

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Neurovascular Unit Dysfunction and Neurodegenerative Disorders

Frontiers in Neuroscience, Год журнала: 2020, Номер 14

Опубликована: Апрель 29, 2020

The neurovascular unit (NVU), comprised of vascular cells, glial cells and neurons, is the minimal functional brain. NVU maintains integrity blood-brain barrier (BBB) regulates supply cerebral blood flow (CBF), both which are keys to maintaining normal brain function. BBB dysfunction a decreased CBF early pathophysiological changes in neurodegenerative disorders, such as Alzheimer's disease (AD), Parkinson's (PD), amyotrophic lateral sclerosis (ALS). In this review, we primarily focus on AD much research has been performed connection between AD. We also discuss role mechanisms PD ALS. As most diseases difficult treat, several potential drug targets that may inform novel vascular-targeted therapies for AD,

Язык: Английский

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Towards a Better Understanding of GABAergic Remodeling in Alzheimer’s Disease

International Journal of Molecular Sciences, Год журнала: 2017, Номер 18(8), С. 1813 - 1813

Опубликована: Авг. 21, 2017

γ-aminobutyric acid (GABA) is the primary inhibitory neurotransmitter in vertebrate brain. In past, there has been a major research drive focused on dysfunction of glutamatergic and cholinergic systems Alzheimer's disease (AD). However, now growing evidence support GABAergic contribution to pathogenesis this neurodegenerative disease. Previous studies paint complex, convoluted often inconsistent picture AD-associated remodeling. Given importance system neuronal function homeostasis, maintenance excitatory/inhibitory balance, processes learning memory, such changes could be an important factor both early later stages AD pathogenesis. limited scope currently available therapies modifying course disease, better understanding remodeling open up innovative novel therapeutic opportunities.

Язык: Английский

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Vascular contributions to Alzheimer's disease

Translational research, Год журнала: 2022, Номер 254, С. 41 - 53

Опубликована: Дек. 15, 2022

Язык: Английский

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Herpes Simplex Virus Type 1 Infection of the Central Nervous System: Insights Into Proposed Interrelationships With Neurodegenerative Disorders

Frontiers in Cellular Neuroscience, Год журнала: 2019, Номер 13

Опубликована: Фев. 26, 2019

Infection with herpes simplex virus type 1 (HSV-1) is highly prevalent in the human population most of infected asymptomatic. Importantly, HSV-1 can infect brain by reaching neurons trigeminal ganglia and without evident clinical symptoms. Once brain, either reside a quiescent latent state this tissue, or eventually actively lead to severe acute necrotizing encephalitis, which characterized exacerbated neuroinflammation prolonged neuroimmune activation producing life-threatening disease. Although encephalitis be treated antivirals that limit replication, neurological sequelae are common will nevertheless remain tissue. there accumulating evidence suggests infection both symptomatic asymptomatic individuals multiple neurodegenerative disorders. Here, we review discuss chronic specific regions how may affect neuron cognitive functions host. We potential cellular molecular mechanisms leading neurodegeneration, such as protein aggregation, dysregulation autophagy, oxidative cell damage apoptosis, among others. Furthermore, impact over inflammation its relationship diseases.

Язык: Английский

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The GABAergic system as a therapeutic target for Alzheimer's disease

Journal of Neurochemistry, Год журнала: 2018, Номер 146(6), С. 649 - 669

Опубликована: Апрель 12, 2018

Glutamatergic and cholinergic dysfunction are well-attested features of Alzheimer's disease (AD), progressing with other pathological indices the disorder exacerbating neuronal network dysfunction. However, relatively little attention has been paid to inhibitory component excitatory/inhibitory (E/I) network, particularly in gamma-aminobutyric acid (GABA) signaling system. There is growing evidence support GABAergic remodeling AD brain, potentially beginning early stages pathogenesis, this could thus be a valid molecular target for drug development pharmacological therapies. Several drugs have tested efficacy attenuating or reversing various symptoms AD, represent novel path by which we might address need more effective benign

Язык: Английский

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