Biological and methodological complexities of beta‐amyloid peptide: Implications for Alzheimer’s disease research DOI Creative Commons
Martyna M. Matuszyk, Claire J. Garwood, Laura Ferraiuolo

et al.

Journal of Neurochemistry, Journal Year: 2021, Volume and Issue: 160(4), P. 434 - 453

Published: Nov. 12, 2021

Although controversial, the amyloid cascade hypothesis remains central to Alzheimer's disease (AD) field and posits amyloid-beta (Aβ) as factor initiating onset. In recent years, there has been an increase in emphasis on studying role of low molecular weight aggregates, such oligomers, which are suggested be more neurotoxic than fibrillary Aβ. Other Aβ isoforms, truncated Aβ, have also implicated disease. However, developing a clear understanding AD pathogenesis hampered by complexity biochemistry vitro vivo. This review explores factors contributing lack consistency experimental approaches taken model aggregation toxicity provides overview different techniques available analyse electron atomic force microscopy, nuclear magnetic resonance spectroscopy, dye-based assays, size exclusion chromatography, mass spectrometry SDS-PAGE. The how types can influence toxicity, leading variation outcomes, further highlighting need for standardisation preparations methods used current research.

Language: Английский

Imaging Techniques in Alzheimer’s Disease: A Review of Applications in Early Diagnosis and Longitudinal Monitoring DOI Open Access
Wieke M. van Oostveen, Elizabeth C. M. de Lange

International Journal of Molecular Sciences, Journal Year: 2021, Volume and Issue: 22(4), P. 2110 - 2110

Published: Feb. 20, 2021

Background. Alzheimer’s disease (AD) is a progressive neurodegenerative disorder affecting many individuals worldwide with no effective treatment to date. AD characterized by the formation of senile plaques and neurofibrillary tangles, followed neurodegeneration, which leads cognitive decline eventually death. Introduction. In AD, pathological changes occur years before onset. Since disease-modifying therapies may be most beneficial in early stages biomarkers for diagnosis longitudinal monitoring progression are essential. Multiple imaging techniques associated used identify monitor AD. Aim. this review, we discuss contemporary regarding their diagnostic utility, benefits limitations. Additionally, novel techniques, applications research assessed. Findings. Reduced hippocampal volume biomarker but atrophy not an AD-specific measure. Hypometabolism temporoparietal regions seen as However, glucose uptake reflects astrocyte function rather than neuronal function. Amyloid-β (Aβ) earliest hallmark can measured positron emission tomography (PET), Aβ accumulation stagnates progresses. Therefore, suitable progression. The measurement tau PET radiotracers exhibited promising results both monitoring, large-scale validation these required. implementation new processing other contribute understanding finding cure. Conclusions. Several proposed all have limitations specificity, reliability sensitivity. Future perspectives. should focus on expanding employment identifying that reflect pathology stages.

Language: Английский

Citations

185
Endo-lysosomal Aβ concentration and pH trigger formation of Aβ oligomers that potently induce Tau missorting DOI Creative Commons
Marie P. Schützmann, Filip Hasecke,

Sarah Bachmann

et al.

Nature Communications, Journal Year: 2021, Volume and Issue: 12(1)

Published: July 30, 2021

Abstract Amyloid-β peptide (Aβ) forms metastable oligomers >50 kDa, termed AβOs, that are more effective than Aβ amyloid fibrils at triggering Alzheimer’s disease-related processes such as synaptic dysfunction and Tau pathology, including mislocalization. In neurons, accumulates in endo-lysosomal vesicles low pH. Here, we show the rate of AβO assembly is accelerated 8,000-fold upon pH reduction from extracellular to pH, expense fibril formation. The pH-induced promotion formation high concentration together enable extensive Aβ42 under physiological conditions. Exploiting enhanced dimeric variant dimAβ furthermore demonstrate targeting AβOs dendritic spines, potent induction missorting, a key factor tauopathies, impaired neuronal activity. results suggest endosomal/lysosomal system major site for pathomechanistically relevant AβOs.

Language: Английский

Citations

92
Lecanemab for early Alzheimer's disease: Appropriate use recommendations from the French federation of memory clinics DOI Creative Commons
Nicolas Villain, Vincent Planche, Matthieu Lilamand

et al.

The Journal of Prevention of Alzheimer s Disease, Journal Year: 2025, Volume and Issue: unknown, P. 100094 - 100094

Published: Feb. 1, 2025

Language: Английский

Citations

1
Zebrafish: A Model Deciphering the Impact of Flavonoids on Neurodegenerative Disorders DOI Creative Commons
Kamel Mhalhel,

Mirea Sicari,

Lidia Pansera

et al.

Cells, Journal Year: 2023, Volume and Issue: 12(2), P. 252 - 252

Published: Jan. 7, 2023

Over the past century, advances in biotechnology, biochemistry, and pharmacognosy have spotlighted flavonoids, polyphenolic secondary metabolites that ability to modulate many pathways involved various biological mechanisms, including those neuronal plasticity, learning, memory. Moreover, flavonoids are known impact processes developing neurodegenerative diseases, namely oxidative stress, neuroinflammation, mitochondrial dysfunction. Thus, several could be used as adjuvants prevent counteract disorders such Alzheimer’s Parkinson’s diseases. Zebrafish is an interesting model organism can offer new opportunities study beneficial effects of on Indeed, high genome homology 70% humans, brain organization largely similar human well neuroanatomical neurochemical processes, neurogenic activity maintained adult makes zebrafish a valuable for diseases deciphering disorders.

Language: Английский

Citations

17
Amyloid-β oligomers interact with NMDA receptors containing GluN2B subunits and metabotropic glutamate receptor 1 in primary cortical neurons: Relevance to the synapse pathology of Alzheimer’s disease DOI Open Access

Kaori Taniguchi,

Fumiko Yamamoto,

Akiko Amano

et al.

Neuroscience Research, Journal Year: 2022, Volume and Issue: 180, P. 90 - 98

Published: March 5, 2022

Language: Английский

Citations

23
In Vivo Near-Infrared Fluorescence Imaging Selective for Soluble Amyloid β Aggregates Using y-Shaped BODIPY Derivative DOI

Takahiro Akasaka,

Hiroyuki Watanabe,

Masahiro Ono

et al.

Journal of Medicinal Chemistry, Journal Year: 2023, Volume and Issue: 66(20), P. 14029 - 14046

Published: Oct. 12, 2023

Soluble amyloid β (Aβ) aggregates, suggested to be the most toxic forms of Aβ, draw attention as therapeutic targets and biomarkers Alzheimer's disease (AD). As soluble Aβ aggregates are transient diverse, imaging their diverse in vivo is expected have a marked impact on research diagnosis AD. Herein, we report near-infrared fluorescent (NIRF) probe, BAOP-16, targeting aggregates. whose molecular shape resembles "y", showed selective increase fluorescence intensity upon binding region high affinity for them. Additionally, BAOP-16 could detect oligomers brains Aβ-inoculated model mice. In an study AD mice displayed significantly higher signals than those wild-type These results indicate that useful NIRF

Language: Английский

Citations

14
Lecanemab: A Second in Class Therapy for the Management of Early Alzheimer’s Disease DOI Creative Commons
Connie H. Yoon,

Corey Groff,

Olivia Criss

et al.

INNOVATIONS in pharmacy, Journal Year: 2024, Volume and Issue: 15(1)

Published: March 18, 2024

The Food and Drug Administration granted traditional approval of lecanemab for the treatment Alzheimer’s disease (AD). Lecanemab is a humanized anti-amyloid monoclonal antibody directed towards Aβ protofibrils. only drug that targets soluble protofils has shown statistical differences in mild AD or cognitive impairment. In its landmark phase III trial, was to slow progression clinical decline, reduction amyloid protein accumulation. difference mean CDR-SOB score improvement between placebo groups -0.45, which significance could be argued. Amyloid burden also considerably reduced as well, but true consequence this remains seen. This beneficial impact on daily living offset by rare serious side effects including amyloid-related imaging abnormalities (ARIA) causing cerebral edema (ARIA-E) microhemorrhages hemosiderin deposits (ARIA-H). Benefits therapy must considered against risk edema. Affordability taken into consideration. current estimated yearly cost twice monthly infusion $26,500. addition significant challenges, frequent infusions may pose concerns related access. Additional agents within class are pipelines with possibly increased efficacy decreased adverse events.

Language: Английский

Citations

5
Anti-amyloid-β Antibodies and Anti-tau Therapies for Alzheimer’s Disease: Recent Advances and Perspectives DOI Open Access

Naoyuki Suzuki,

T. Hatta,

Mana Ito

et al.

Chemical and Pharmaceutical Bulletin, Journal Year: 2024, Volume and Issue: 72(7), P. 602 - 609

Published: June 30, 2024

Amyloid-β (Aβ) plaques and neurofibrillary tangles containing phosphorylated tau protein are major hallmarks of Alzheimer's disease (AD). Drug discovery efforts to target Aβ have been the primary focus for several decades. Recently, substantial breakthroughs achieved in clinical development antibodies; aducanumab was approved under conditional accelerated pathway by Food Administration (FDA) U.S. as first disease-modifying agent treating AD, lecanemab has granted traditional full Japan. In addition, donanemab met endpoint a phase 3 study. On other hand, tau-targeting therapies failed show benefit although that increased levels strong correlation with cognitive impairment relative depositions. Currently, immunotherapies, such anti-tau antibodies vaccines, shown functional benefits trials. Also, trials combination therapy see their potential being investigated. this review, we provide updates on results anti-Aβ therapeutics suggest future directions these therapeutics.

Language: Английский

Citations

5
An Expanded Narrative Review of Neurotransmitters on Alzheimer’s Disease: The Role of Therapeutic Interventions on Neurotransmission DOI Creative Commons
Enes Akyüz, Alina Arulsamy, Feyza Şule Aslan

et al.

Molecular Neurobiology, Journal Year: 2024, Volume and Issue: unknown

Published: July 16, 2024

Alzheimer's disease (AD) is a progressive neurodegenerative disease. The accumulation of amyloid-β (Aβ) plaques and tau neurofibrillary tangles are the key players responsible for pathogenesis Aβ affect balance in chemical neurotransmitters brain. Thus, current review examined role discusses alterations neurochemical activity cross talk with their receptors transporters. In presence tangles, changes may occur expression neuronal which turn triggers excessive release glutamate into synaptic cleft contributing to cell death damage. GABAergic system also be affected by AD pathology similar way. addition, decreased cholinergic dysfunction dopamine neurotransmission contribute damage cognitive function. Moreover, deficiencies noradrenergic neurons within locus coeruleus suggests that stimulation could useful addressing its pathophysiology. regulation melatonin, known effectiveness enhancing function preventing accumulation, along involvement serotonergic histaminergic cognition memory, becomes remarkable promoting AD. Additionally, nitric oxide adenosine-based therapeutic approaches play protective neuroinflammation. Overall, neurotransmitter-based strategies emerge as pivotal neurotransmitter homeostasis context This discussed potential drugs effective slowing correcting processes targeting imbalance Therefore, serve future strategy tackle

Language: Английский

Citations

5
The Role of Lipid Environment in Ganglioside GM1-Induced Amyloid β Aggregation DOI Creative Commons
Vladimı́r Rudajev, Jiřı́ Novotný

Membranes, Journal Year: 2020, Volume and Issue: 10(9), P. 226 - 226

Published: Sept. 9, 2020

Ganglioside GM1 is the most common brain ganglioside enriched in plasma membrane regions known as lipid rafts or microdomains. participates many modulatory and communication functions associated with development, differentiation, protection of neuronal tissue. It has, however, been demonstrated that plays a negative role pathophysiology Alzheimer’s disease (AD). The two features AD are formation intracellular neurofibrillary bodies accumulation extracellular amyloid β (Aβ). Aβ peptide characterized by intrinsic conformational flexibility. Depending on its partners, can adopt different spatial arrangements. has shown to induce specific changes organization Aβ, which lead enhanced deleterious effect especially membranes containing clusters this ganglioside. Changes levels distribution during development may contribute aggravation disease.

Language: Английский

Citations

35