Characterization of Amyloid-β Plaques and Autofluorescent Lipofuscin Aggregates in Alzheimer’s Disease Brain: A Confocal Microscopy Approach

Kun, Alejandra; González-Camacho, Fernando; Hernández, Sílvia; Moreno-García, Alexandra; Calero, Olga; Calero, Miguel

doi:10.1007/978-1-4939-7816-8_31

Cited by 12 publications

(8 citation statements)

References 18 publications

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“…For example, DNA probes emitting in the far-red range can be combined with the detection of LF in both green and red channels (Zheng et al, 2010 ). Recently, we have developed a method based on channel filtering of confocal microscopy to identify and discriminate LF autofluorescence signals from the specific ones, such as amyloid plaques in the AD brain (see Figure 1 ) (Kun et al, 2018 ).…”

Section: Lipofuscin Composition and Distributionmentioning

confidence: 99%

An Overview of the Role of Lipofuscin in Age-Related Neurodegeneration

et al. 2018

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Despite aging being by far the greatest risk factor for highly prevalent neurodegenerative disorders, the molecular underpinnings of age-related brain changes are still not well understood, particularly the transition from normal healthy brain aging to neuropathological aging. Aging is an extremely complex, multifactorial process involving the simultaneous interplay of several processes operating at many levels of the functional organization. The buildup of potentially toxic protein aggregates and their spreading through various brain regions has been identified as a major contributor to these pathologies. One of the most striking morphologic changes in neurons during normal aging is the accumulation of lipofuscin (LF) aggregates, as well as, neuromelanin pigments. LF is an autofluorescent lipopigment formed by lipids, metals and misfolded proteins, which is especially abundant in nerve cells, cardiac muscle cells and skin. Within the Central Nervous System (CNS), LF accumulates as aggregates, delineating a specific senescence pattern in both physiological and pathological states, altering neuronal cytoskeleton and cellular trafficking and metabolism, and being associated with neuronal loss, and glial proliferation and activation. Traditionally, the accumulation of LF in the CNS has been considered a secondary consequence of the aging process, being a mere bystander of the pathological buildup associated with different neurodegenerative disorders. Here, we discuss recent evidence suggesting the possibility that LF aggregates may have an active role in neurodegeneration. We argue that LF is a relevant effector of aging that represents a risk factor or driver for neurodegenerative disorders.

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Section: Lipofuscin Composition and Distributionmentioning

confidence: 99%

An Overview of the Role of Lipofuscin in Age-Related Neurodegeneration

et al. 2018

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“…The hypothesis of free radical damage in AD postulates that (Cabungcal et al, 2013) the body's defense systems are weakened with disease progression, causing the accumulation of a pathologically high level of free radicals, which react with unsaturated fatty acids in the cell membrane to form lipid peroxides such as malondialdehyde. Malondialdehyde combines with proteins, nucleic acids, and other biological macromolecules to form insoluble lipofuscin deposits in cells (Kun et al, 2018). Lipofuscin can damage cell structure, disrupt cell metabolism, accelerate cell senescence and death, as well as affect learning and memory (Giaccone et al, 2011;Kwon et al, 2016).…”

Section: The Ecm Resists Oxidative Stress and Reduces Ad Damagementioning

confidence: 99%

Role of the Extracellular Matrix in Alzheimer’s Disease

Sun

Jiang

et al. 2021

Front. Aging Neurosci.

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Alzheimer’s disease (AD) is a neurodegenerative disease with complex pathological characteristics, whose etiology and pathogenesis are still unclear. Over the past few decades, the role of the extracellular matrix (ECM) has gained importance in neurodegenerative disease. In this review, we describe the role of the ECM in AD, focusing on the aspects of synaptic transmission, amyloid-β-plaque generation and degradation, Tau-protein production, oxidative-stress response, and inflammatory response. The function of ECM in the pathological process of AD will inform future research on the etiology and pathogenesis of AD.

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“…One additional interesting observation was the increased presence of autofluorescent aggregates as ageing progressed. These aggregates resemble lipofuscin in appearance and properties (wide fluorescence emission range; Fahim & Robbins, 1982; Kun et al., 2018). It has previously been reported that the appearance of lipofuscin is associated with ageing (Terman & Brunk, 1998, 2004, 2005; Terman et al., 2010).…”

Section: Discussionmentioning

confidence: 99%

A cross‐sectional study of ageing at the mouse neuromuscular junction and effects of an experimental therapeutic approach for dynapenia

Li,

Patel,

Baroudi

et al. 2023

The Journal of Physiology

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Despite prior efforts to understand and target dynapenia (age‐induced loss of muscle strength), this condition remains a major challenge that reduces the quality of life in the aged population. We have focused on the neuromuscular junction (NMJ) where changes in structure and function have rarely been systematically studied as a dynamic and progressive process. Our cross‐sectional study found neurotransmission at the male mouse NMJ to be biphasic, displaying an early increase followed by a later decrease, and this phenotype was associated with structural changes to the NMJ. A cross‐sectional characterization showed that age‐induced alterations fell into four age groups: young adult (3–6 months), adult (7–18 months), early aged (19–24 months), and later aged (25–30 months). We then utilized a small molecule therapeutic candidate, GV‐58, applied acutely during the later aged stage to combat age‐induced reductions in transmitter release by increasing calcium influx during an action potential, which resulted in a significant increase in transmitter release. This comprehensive study of neuromuscular ageing at the NMJ will enable future research to target critical time points for therapeutic intervention. imageKey points Age‐induced frailty and falls are the leading causes of injury‐related death and are caused by an age‐induced loss of muscle strength due to a combination of neurological and muscular changes. A cross‐sectional approach was used to study age‐induced changes to the neuromuscular junction in a mouse model, and physiological changes that were biphasic over the ageing time course were found. Changes in physiology at the neuromuscular junction were correlated with alterations in neuromuscular junction morphology. An acutely applied positive allosteric gating modifier of presynaptic voltage‐gated calcium channels was tested as a candidate therapeutic strategy that could increase transmitter release at aged neuromuscular junctions. These results provide a detailed time course of age‐induced changes at the neuromuscular junction in a mouse model and test a candidate therapeutic strategy for weakness.

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Characterization of Amyloid-β Plaques and Autofluorescent Lipofuscin Aggregates in Alzheimer’s Disease Brain: A Confocal Microscopy Approach

Cited by 12 publications

References 18 publications

An Overview of the Role of Lipofuscin in Age-Related Neurodegeneration

An Overview of the Role of Lipofuscin in Age-Related Neurodegeneration

Role of the Extracellular Matrix in Alzheimer’s Disease

A cross‐sectional study of ageing at the mouse neuromuscular junction and effects of an experimental therapeutic approach for dynapenia

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