Alzheimer's disease: Potential pathogenesis and imaging findings DOI Creative Commons
Yan Zhang, Chenpeng Zhang, Jianjun Liu

et al.

View, Journal Year: 2023, Volume and Issue: 4(5)

Published: May 25, 2023

Abstract Alzheimer's disease (AD) is a common neurodegenerative disease. The histopathological changes in AD include amyloid β‐protein (Aβ) deposition, tau tangles, neuroinflammation, and neurodegeneration. Some of the pathological could be shown vivo by positron emission tomography (PET) magnetic resonance imaging (MRI) biomarkers, which play key role diagnosing AD. Fluorodeoxyglucose (FDG‐PET) can reflect predict dysfunction. Aβ‐PET sensitive for diagnosis early but cannot distinguish severity Tau‐PET compensate deficiency Aβ‐PET. Tau tangles are positively correlated with associated cognitive impairment. Probes targeting neuroinflammation have been developed, further study needed to validate their effectiveness. Conventional MRI performs high tissue contrast that show structural has routinely applied clinical practice, such as evaluation cerebral atrophy. Advanced sequences (such diffusion tensor imaging, arterial spin labeling, spectroscopy, blood oxygenation level dependent, quantitative susceptibility mapping) provide additional information beyond structure includes brain microstructure, perfusion, metabolite concentration, activity, connections networks between regions, iron etc. Integrated PET may improve diagnostic efficiency

Language: Английский

Anti-inflammatory role of gold nanoparticles in the prevention and treatment of Alzheimer's disease DOI Creative Commons

Munire Aili,

Kebing Zhou,

Jun Zhan

et al.

Journal of Materials Chemistry B, Journal Year: 2023, Volume and Issue: 11(36), P. 8605 - 8621

Published: Jan. 1, 2023

Alzheimer's disease (AD) is a neurodegenerative that causes memory and cognitive dysfunction reduces person's decision-making reasoning functions. AD the leading cause of dementia in elderly. Patients with have increased expression pro-inflammatory cytokines nervous system, sustained inflammatory response impairs neuronal function. Meanwhile, long-term use anti-inflammatory drugs can reduce incidence to some extent. This confirms anti-neuroinflammation may be an effective treatment for AD. Gold nanoparticles (AuNPs) are emerging nanomaterial promising physicochemical properties, antioxidant. AuNPs neuroinflammation by inducing macrophage polarization toward M2 phenotype, reducing cytokine expression, blocking leukocyte adhesion, decreasing oxidative stress. Therefore, gradually attracting interest scholars used treating diseases drug delivery. Herein, we explored role mechanism The topic worth exploring future, not only help solve global public health problem but also provide reference other neuroinflammatory diseases.

Language: Английский

Citations

26
Recent Development in the Understanding of Molecular and Cellular Mechanisms Underlying the Etiopathogenesis of Alzheimer’s Disease DOI Open Access
Atefeh Afsar, Maria del Carmen Chacon Castro,

Adedamola Saidi Soladogun

et al.

International Journal of Molecular Sciences, Journal Year: 2023, Volume and Issue: 24(8), P. 7258 - 7258

Published: April 14, 2023

Alzheimer's disease (AD) is a progressive neurodegenerative disorder that leads to dementia and patient death. AD characterized by intracellular neurofibrillary tangles, extracellular amyloid beta (Aβ) plaque deposition, neurodegeneration. Diverse alterations have been associated with progression, including genetic mutations, neuroinflammation, blood-brain barrier (BBB) impairment, mitochondrial dysfunction, oxidative stress, metal ion imbalance.Additionally, recent studies shown an association between altered heme metabolism AD. Unfortunately, decades of research drug development not produced any effective treatments for Therefore, understanding the cellular molecular mechanisms underlying pathology identifying potential therapeutic targets are crucial development. This review discusses most common promising discovery. Furthermore, it highlights role in summarizes mathematical models AD, stochastic model effect Aβ on We also summarize treatment strategies these can offer clinical trials.

Language: Английский

Citations

23
The role of high mobility group box 1 in neuroinflammatory related diseases DOI Open Access

Jialu Mo,

Jiao Hu,

Xianglin Cheng

et al.

Biomedicine & Pharmacotherapy, Journal Year: 2023, Volume and Issue: 161, P. 114541 - 114541

Published: March 22, 2023

High mobility group box 1 (HMGB1) is a ubiquitous and highly conserved non-histone DNA-binding protein with different biological functions according to its subcellular localization. It widely believed that HMGB1, which released into the extracellular space, plays key role in inflammatory response. In recent years, numerous studies have shown development of various neurological diseases such as epilepsy, Alzheimer's disease (AD), Parkinson's (PD), amyotrophic lateral sclerosis (ALS), multiple (MS), cerebrovascular traumatic brain injury (TBI) are inextricably linked inflammation. We will review mechanisms HMGB1 receptors nervous system inflammation provide basis for further new HMGB1-based therapies.

Language: Английский

Citations

22
The Brain–Gut Axis, an Important Player in Alzheimer and Parkinson Disease: A Narrative Review DOI Open Access
Eugenio Caradonna,

Raffaello Nemni,

Angelo Bifone

et al.

Journal of Clinical Medicine, Journal Year: 2024, Volume and Issue: 13(14), P. 4130 - 4130

Published: July 15, 2024

Neurodegenerative diseases, such as Alzheimer’s disease (AD) and Parkinson’s (PD), are severe age-related disorders with complex multifactorial causes. Recent research suggests a critical link between neurodegeneration the gut microbiome, via gut–brain communication pathway. This review examines role of trimethylamine N-oxide (TMAO), microbiota-derived metabolite, in development AD PD, investigates its interaction microRNAs (miRNAs) along this bidirectional TMAO, which is produced from dietary metabolites like choline carnitine, has been linked to increased neuroinflammation, protein misfolding, cognitive decline. In AD, elevated TMAO levels associated amyloid-beta tau pathologies, blood–brain barrier disruption, neuronal death. can cross promote aggregation amyloid proteins. Similarly, affects alpha-synuclein conformation aggregation, hallmark PD. also activates pro-inflammatory pathways NF-kB signaling, exacerbating neuroinflammation further. Moreover, modulates expression various miRNAs that involved neurodegenerative processes. Thus, microbiome–miRNA–brain axis represents newly discovered mechanistic dysbiosis neurodegeneration. MiRNAs regulate key oxidative stress, death, contributing progression. As direct consequence, specific miRNA signatures may serve potential biomarkers for early detection monitoring PD aims elucidate interrelationships microbiota, trimethylamine-N-oxide (miRNAs), central nervous system, implications these connections diseases. context, an overview current neuroradiology techniques available studying animal models used investigate intricate pathologies will be provided. summary, bulk evidence supports concept modulating pathway through changes, manipulation and/or miRNA-based therapies offer novel approaches implementing treatment debilitating neurological disorders.

Language: Английский

Citations

12
Investigating White Matter Neuroinflammation in Alzheimer Disease Using Diffusion-Based Neuroinflammation Imaging DOI
Qing Wang, Suzanne E. Schindler, Gengsheng Chen

et al.

Neurology, Journal Year: 2024, Volume and Issue: 102(4)

Published: Feb. 5, 2024

Alzheimer disease (AD) is primarily associated with accumulations of amyloid plaques and tau tangles in gray matter, however, it now acknowledged that neuroinflammation, particularly white matter (WM), significantly contributes to the development progression AD. This study aims investigate WM neuroinflammation continuum AD its association pathologies cognition using diffusion-based imaging (NII).

Language: Английский

Citations

11
Microglia measured by TSPO PET are associated with Alzheimer's disease pathology and mediate key steps in a disease progression model DOI Creative Commons
Samantha Rossano, Aubrey S. Johnson, Anna Smith

et al.

Alzheimer s & Dementia, Journal Year: 2024, Volume and Issue: 20(4), P. 2397 - 2407

Published: Feb. 1, 2024

Abstract INTRODUCTION Evidence suggests microglial activation precedes regional tau and neurodegeneration in Alzheimer's disease (AD). We characterized microglia with translocator protein (TSPO) positron emission tomography (PET) within an AD progression model where global amyloid beta (Aβ) local neurodegeneration, resulting cognitive impairment. METHODS Florbetaben, PBR28, MK‐6240 PET, T1 magnetic resonance imaging, measures were performed 19 cognitively unimpaired older adults 22 patients mild impairment or to examine associations among activation, Aβ, tau, cognition, adjusting for neurodegeneration. Mediation analyses evaluated the possible role of along model. RESULTS Higher PBR28 uptake was associated higher lower MMSE score, independent mediated between early middle Braak stages, cognition. DISCUSSION Microglia are pathology cognition may mediate relationships subsequent steps progression.

Language: Английский

Citations

8
Biomarkers for Alzheimer’s Disease: Context of Use, Qualification, and Roadmap for Clinical Implementation DOI Creative Commons
Jeffrey L. Cummings,

Jefferson W. Kinney

Medicina, Journal Year: 2022, Volume and Issue: 58(7), P. 952 - 952

Published: July 19, 2022

: The US Food and Drug Administration (FDA) defines a biomarker as characteristic that is measured an indicator of normal biological processes, pathogenic or responses to exposure intervention. Biomarkers may be used in clinical care drug development tools (DDTs) trials. goal this review perspective provide insight into the regulatory guidance for use biomarkers trials care.

Language: Английский

Citations

33
Neuroinflammation, Its Role in Alzheimer’s Disease and Therapeutic Strategies DOI Creative Commons

Marianna Király,

Joseph F. Foss, Thomas J. Giordano

et al.

The Journal of Prevention of Alzheimer s Disease, Journal Year: 2023, Volume and Issue: unknown

Published: Jan. 1, 2023

Neuroinflammation precedes the clinical onset of various neurodegenerative diseases, including Alzheimer's disease (AD), by years or frequently even decades (1-3). In terms underlying physiology, there is a great need for understanding and controlling interactions between central nervous system (CNS) immune in an attempt to develop approaches prevent delay disease's progression. Nerve cells have limited motion capability, whereas can migrate freely via circulation. This difference raises variety questions context senile plaque formation phagocytosis. Broad-scale unbiased genomic studies bring several genetic variants such as sialic acid binding Ig-like lectin 3 (CD33), triggering receptor expressed on myeloid 2 (TREM2) complement type 1 (CR1) into focus researchers' attention potential risk factors neuroinflammation. addition, advanced proteomic analyses been revealing links these contributors complex, malfunctioning signaling pathways (including upregulation like tumor necrosis factor TNF-α, growth TGF-β interleukin IL-1α) that promote proinflammatory mechanisms intracellular trafficking, synaptic function, cell metabolism/ proliferation. AD, brain's microglia astrocytes, which are normally responsible maintaining homeostasis transmission its remodeling pruning, initiators neuroinflammation toxic tau amyloid-β (Aβ) accumulation. Thus, they drive CNS state sustained self-accelerated deterioration. Here we aim review types mediators involved symptom manifestation settings, candidates improving diagnosis treatment.

Language: Английский

Citations

18
HIF-1α serves as a co-linker between AD and T2DM DOI Open Access
Yang Hai, Ke Ren, Yarong Zhang

et al.

Biomedicine & Pharmacotherapy, Journal Year: 2024, Volume and Issue: 171, P. 116158 - 116158

Published: Jan. 18, 2024

Alzheimer's disease (AD)-related brain deterioration is linked to the type 2 diabetes mellitus (T2DM) features hyperglycemia, hyperinsulinemia, and insulin resistance. Hypoxia as a common risk factor for both AD T2DM. Hypoxia-inducible factor-1 alpha (HIF-1α) acts main regulator of hypoxia response may be key target in comorbidity HIF-1α expression closely related resistance, inflammation. Tissue oxygen consumption disrupts homeostasis, leading increased reactive species levels inhibition receptor pathway activity, causing neuroinflammation, abnormal Aβ deposition, tau hyperphosphorylation. activation also leads deposition by promoting shearing amyloid precursor protein inhibiting degradation Aβ, it promotes hyperphosphorylation activating oxidative stress astrocytes, which further exasperates AD. Therefore, we believe that HIF-α has great potential treatment Importantly, intracellular homeostasis more crucial than its level.

Language: Английский

Citations

7
Relationship Between Reactive Astrocytes, by [18F]SMBT-1 Imaging, with Amyloid-Beta, Tau, Glucose Metabolism, and TSPO in Mouse Models of Alzheimer’s Disease DOI Creative Commons
Yanyan Kong,

Cinzia Maschio,

Xuefeng Shi

et al.

Molecular Neurobiology, Journal Year: 2024, Volume and Issue: 61(10), P. 8387 - 8401

Published: March 19, 2024

Reactive astrocytes play an important role in the development of Alzheimer's disease (AD). Here, we aimed to investigate temporospatial relationships among monoamine oxidase-B, tau and amyloid-β (Aβ), translocator protein, glucose metabolism by using multitracer imaging AD transgenic mouse models. Positron emission tomography (PET) with [

Language: Английский

Citations

7