Comprehensive Review on Alzheimer’s Disease: Causes and Treatment

Molecules, Journal Year: 2020, Volume and Issue: 25(24), P. 5789 - 5789

Published: Dec. 8, 2020

Alzheimer’s disease (AD) is a disorder that causes degeneration of the cells in brain and it main cause dementia, which characterized by decline thinking independence personal daily activities. AD considered multifactorial disease: two hypotheses were proposed as for AD, cholinergic amyloid hypotheses. Additionally, several risk factors such increasing age, genetic factors, head injuries, vascular diseases, infections, environmental play role disease. Currently, there are only classes approved drugs to treat including inhibitors cholinesterase enzyme antagonists N-methyl d-aspartate (NMDA), effective treating symptoms but do not cure or prevent Nowadays, research focusing on understanding pathology targeting mechanisms, abnormal tau protein metabolism, β-amyloid, inflammatory response, free radical damage, aiming develop successful treatments capable stopping modifying course AD. This review discusses currently available future theories development new therapies disease-modifying therapeutics (DMT), chaperones, natural compounds.

Language: Английский

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Hippocampal sharp wave‐ripple: A cognitive biomarker for episodic memory and planning

Hippocampus, Journal Year: 2015, Volume and Issue: 25(10), P. 1073 - 1188

Published: July 2, 2015

ABSTRACT Sharp wave ripples (SPW‐Rs) represent the most synchronous population pattern in mammalian brain. Their excitatory output affects a wide area of cortex and several subcortical nuclei. SPW‐Rs occur during “off‐line” states brain, associated with consummatory behaviors non‐REM sleep, are influenced by numerous neurotransmitters neuromodulators. They arise from recurrent system CA3 region SPW‐induced excitation brings about fast network oscillation (ripple) CA1. The spike content is temporally spatially coordinated consortium interneurons to replay fragments waking neuronal sequences compressed format. assist transferring this hippocampal representation distributed circuits support memory consolidation; selective disruption interferes memory. Recently acquired pre‐existing information combined SPW‐R influence decisions, plan actions and, potentially, allow for creative thoughts. In addition widely studied contribution memory, may also affect endocrine function via activation hypothalamic circuits. Alteration physiological mechanisms supporting leads their pathological conversion, “p‐ripples,” which marker epileptogenic tissue can be observed rodent models schizophrenia Alzheimer's Disease. Mechanisms genesis discussed review. © 2015 Authors Hippocampus Published Wiley Periodicals, Inc.

Language: Английский

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Alzheimer disease

Nature Reviews Disease Primers, Journal Year: 2021, Volume and Issue: 7(1)

Published: May 13, 2021

Language: Английский

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Oxidative Stress, Synaptic Dysfunction, and Alzheimer’s Disease

Journal of Alzheimer s Disease, Journal Year: 2017, Volume and Issue: 57(4), P. 1105 - 1121

Published: Jan. 6, 2017

Alzheimer's disease (AD) is a devastating neurodegenerative disorder without cure. Most AD cases are sporadic where age represents the greatest risk factor. Lack of understanding mechanism hinders development efficacious therapeutic approaches. The loss synapses in affected brain regions correlates best with cognitive impairment patients and has been considered as early that precedes neuronal loss. Oxidative stress recognized contributing factor aging progression multiple diseases including AD. Increased production reactive oxygen species (ROS) associated age- disease-dependent mitochondrial function, altered metal homeostasis, reduced antioxidant defense directly affect synaptic activity neurotransmission neurons leading to dysfunction. In addition, molecular targets by ROS include nuclear DNA, lipids, proteins, calcium dynamics cellular architecture, receptor trafficking endocytosis, energy homeostasis. Abnormal metabolism turn could accumulation amyloid-β (Aβ) hyperphosphorylated Tau protein, which independently exacerbate dysfunction production, thereby vicious cycle. While mounting evidence implicates etiology, clinical trials therapies have not produced consistent results. this review, we will discuss role oxidative AD, innovative strategies evolved based on better complexity mechanisms dual play health disease.

Language: Английский

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Clearance systems in the brain—implications for Alzheimer disease

Nature Reviews Neurology, Journal Year: 2015, Volume and Issue: 11(8), P. 457 - 470

Published: July 21, 2015

Language: Английский

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New Technologies for Analysis of Extracellular Vesicles

Chemical Reviews, Journal Year: 2018, Volume and Issue: 118(4), P. 1917 - 1950

Published: Jan. 31, 2018

Extracellular vesicles (EVs) are diverse, nanoscale membrane actively released by cells. Similar-sized can be further classified (e.g., exosomes, microvesicles) based on their biogenesis, size, and biophysical properties. Although initially thought to cellular debris, thus under-appreciated, EVs now increasingly recognized as important vehicles of intercellular communication circulating biomarkers for disease diagnoses prognosis. Despite clinical potential, the lack sensitive preparatory analytical technologies poses a barrier translation. New platforms including molecular ones being developed address these challenges. Recent advances in field expected have far-reaching impact both basic translational studies. This article aims present comprehensive critical overview emerging EV detection applications.

Language: Английский

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PET Imaging of Tau Deposition in the Aging Human Brain

Neuron, Journal Year: 2016, Volume and Issue: 89(5), P. 971 - 982

Published: March 1, 2016

Language: Английский

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Tau PET patterns mirror clinical and neuroanatomical variability in Alzheimer’s disease

Brain, Journal Year: 2016, Volume and Issue: 139(5), P. 1551 - 1567

Published: March 8, 2016

SEE SARAZIN ET AL DOI101093/BRAIN/AWW041 FOR A SCIENTIFIC COMMENTARY ON THIS ARTICLE: The advent of the positron emission tomography tracer (18)F-AV1451 provides unique opportunity to visualize regional distribution tau pathology in living human brain. In this study, we tested hypothesis that is closely linked symptomatology and patterns glucose hypometabolism Alzheimer's disease, contrast more diffuse amyloid-β pathology. We included 20 patients meeting criteria for probable disease dementia or mild cognitive impairment due presenting with a variety clinical phenotypes, 15 amyloid-β-negative cognitively normal individuals, who underwent (tau), (11)C-PiB (amyloid-β) (18)F-FDG (glucose metabolism) tomography, apolipoprotein E (APOE) genotyping neuropsychological testing. Voxel-wise contrasts against controls (at P < 0.05 family-wise error corrected) showed posterior cortical atrophy ('visual variant disease', n = 7) specifically targeted clinically affected brain regions, while bound diffusely throughout neocortex. Patients an amnestic-predominant presentation (n 5) highest retention medial temporal lateral temporoparietal regions. logopenic primary progressive aphasia ('language demonstrated asymmetric left greater than right hemisphere uptake three five patients. Across 30 FreeSurfer-defined regions interest 16 all scans available, there was strong negative association between (Pearson's r -0.49 ± 0.07, 0.001) less pronounced positive associations 0.16 0.09, 0.18 0.001). linear regressions thresholded at (uncorrected) that, across patients, younger age associated wide neocortex, older increased lobe. APOE ϵ4 carriers parietal non-carriers. Finally, worse performance on domain-specific tests key implicated memory (medial lobes), visuospatial function (occipital, cortex) language (left > cortex). conclusion, imaging-contrary imaging-shows anatomical heterogeneity disease. Although preliminary, these results are consistent expand upon findings from post-mortem, animal cerebrospinal fluid studies, suggest pathological aggregation neurodegeneration manifestations

Language: Английский

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Hallmarks of neurodegenerative diseases

Cell, Journal Year: 2023, Volume and Issue: 186(4), P. 693 - 714

Published: Feb. 1, 2023

Summary

Decades of research have identified genetic factors and biochemical pathways involved in neurodegenerative diseases (NDDs). We present evidence for the following eight hallmarks NDD: pathological protein aggregation, synaptic neuronal network dysfunction, aberrant proteostasis, cytoskeletal abnormalities, altered energy homeostasis, DNA RNA defects, inflammation, cell death. describe hallmarks, their biomarkers, interactions as a framework to study NDDs using holistic approach. The can serve basis defining pathogenic mechanisms, categorizing different based on primary stratifying patients within specific NDD, designing multi-targeted, personalized therapies effectively halt NDDs.

Language: Английский

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SynGO: An Evidence-Based, Expert-Curated Knowledge Base for the Synapse

Neuron, Journal Year: 2019, Volume and Issue: 103(2), P. 217 - 234.e4

Published: June 3, 2019

Language: Английский

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