Perspectives on Aging and Quality of Life

Healthcare, Год журнала: 2023, Номер 11(15), С. 2131 - 2131

Опубликована: Июль 26, 2023

The aging of the world's population and health problems accompanying it are becoming increasingly severe. Healthcare policies in developed countries focus on how to prevent treat diseases associated with maintain quality life. Typical age-related include deafness, cataracts, osteoarthritis, chronic obstructive pulmonary disease, diabetes mellitus, dementia. Although mechanisms by which these develop differ, they all caused accumulation molecular cellular damage over time. In addition, can cause a decline physical mental functions ability perform activities daily living, as well loss roles society sense fulfillment Therefore, there is need for treatment measures accurately grasp This review aims introduce areas representative papers expected be contributed special issue "Aging Quality Life".

Язык: Английский

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Hypothesis review: Alzheimer's overture guidelines

Brain Pathology, Год журнала: 2022, Номер 33(1)

Опубликована: Окт. 12, 2022

Abstract National Institute on Aging–Alzheimer's Association definition and classification of sporadic Alzheimer's disease (sAD) is based the assumption that β‐amyloid drives pathogenesis sAD, therefore, pathology sine‐qua‐non condition for diagnosis sAD. The neuropathological concurrence senile plaques (SPs) neurofibrillary tangles (NFTs) designated as changes. However, NFTs develop in brain decades before appearance SPs, their distribution does not parallel SPs. Moreover, are found about 85% individuals at age 65 around 97% 80. SPs occur 30% 50%–60% More than 70 genetic risk factors have been identified sAD; encoded proteins modulate cell membranes, synapses, lipid metabolism, neuroinflammation. (AD) overture provides a new concept aging sAD further discussion. AD proposes is: (i) multifactorial progressive neurodegenerative biological process, (ii) characterized by early 3R + 4Rtau NFTs, (iii) later deposition (iv) with particular non‐overlapped regional (v) preceded or occurring molecular changes affecting cytoskeleton, protein energy neuroinflammation, cycle, astrocytes, microglia, blood vessels; (vi) accompanied neuron loss atrophy, (vii) prevalent human aging, (viii) manifested pre‐clinical AD, progressing universally to mild cognitive impairment due mild, moderate, severe dementia.

Язык: Английский

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Anti-Amyloid Therapies for Alzheimer’s Disease and the Amyloid Cascade Hypothesis

International Journal of Molecular Sciences, Год журнала: 2023, Номер 24(19), С. 14499 - 14499

Опубликована: Сен. 24, 2023

Over the past 30 years, majority of (pre)clinical efforts to find an effective therapy for Alzheimer’s disease (AD) focused on clearing β-amyloid peptide (Aβ) from brain since, according amyloid cascade hypothesis, was (and it is still considered by many) pathogenic determinant this neurodegenerative disorder. However, as reviewed in article, results numerous clinical trials that have tested anti-Aβ therapies date indicate plays a minor role pathogenesis AD. Indeed, even Aducanumab and Lecanemab, two antibodies recently approved FDA AD therapy, well Donanemab showed limited efficacy cognitive parameters phase III trials, despite their capability markedly lowering Aβ load. Furthermore, preclinical evidence demonstrates possesses several physiological functions, including memory formation, suggesting may part be due loss function peptide. Finally, generally accepted could result many molecular dysfunctions, therefore, if we keep chasing only Aβ, means cannot see forest trees.

Язык: Английский

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Controversial Past, Splendid Present, Unpredictable Future: A Brief Review of Alzheimer Disease History

Journal of Clinical Medicine, Год журнала: 2024, Номер 13(2), С. 536 - 536

Опубликована: Янв. 17, 2024

Background: The concept of Alzheimer disease (AD)—since its histological discovery by to the present day—has undergone substantial modifications. Methods: We conducted a classical narrative review this field with bibliography selection (giving preference Medline best match). Results: following subjects are reviewed and discussed: Alzheimer’s discovery, Kraepelin’s creation new that was rare condition until 1970′s, growing interest investment in AD as major killer society large elderly population second half 20th century, consolidation clinicopathological model, modern nosology based on dominant amyloid hypothesis among many others. In 21st development biomarkers has supported novel biological definition AD, although proposed therapies have failed cure disease. incidence dementia/AD shown decrease affluent countries (possibly due control risk factors), mixed dementia been established most frequent etiology oldest old. Conclusions: current lacks unanimity. Many hypotheses attempt explain complex physiopathology entwined aging, cascade yielded poor therapeutic results. reduction appears promising but it should be confirmed future. A reevaluation is also necessary.

Язык: Английский

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Ether Lipid-Mediated Antioxidant Defense in Alzheimer’s Disease

Antioxidants, Год журнала: 2023, Номер 12(2), С. 293 - 293

Опубликована: Янв. 28, 2023

One of the richest tissues in lipid content and diversity human body is brain. The brain constitutively highly vulnerable to oxidative stress. This stress a determinant aging, as well onset progression sporadic (late-onset) Alzheimer's disease (sAD). Glycerophospholipids are main category widely distributed neural cell membranes, with very significant presence for ether subclass. Ether lipids have played key role evolution compositional specificity functionality. determine membrane structural functional properties, trafficking, signaling antioxidant defense mechanisms. Here, we explore idea that actively participate pathogenesis sAD. Firstly, evaluate quantitative relevance composition, their evolution. Then, analyze implications physiology, highlighting inherent properties. Finally, discuss changes associated sAD physiopathological implications, propose mechanism that, vicious cycle, explains potential significance

Язык: Английский

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Multiple system atrophy with amyloid-β-predominant Alzheimer’s disease neuropathologic change

Brain Communications, Год журнала: 2024, Номер 6(3)

Опубликована: Янв. 1, 2024

Abstract Multiple system atrophy is a neurodegenerative disease with α-synuclein pathology predominating in the striatonigral and olivopontocerebellar systems. Mixed pathologies are considered to be of low frequency mostly comprise primary age-related tauopathy or levels Alzheimer’s disease-related neuropathologic change. Therefore, concomitant presence different misfolded proteins same brain region less likely multiple atrophy. During neuropathological evaluation 21 consecutive cases, we identified four cases exhibiting an unusual discrepancy between high Thal amyloid-β phase transentorhinal Braak neurofibrillary tangle stage. We mapped pathology, measured size number glial cytoplasmic inclusions compared peptides disease. In addition, performed seeding assay from affected putamen samples. genetic testing for APOE, MAPT, PSEN1, PSEN2 APP. refer tau as ‘amyloid-β-predominant change-multiple atrophy’ distinguish these typical As most mixed reported literature, did not show peculiar clinical MRI profile. Three amyloid-β-predominant were available testing, all carried APOE ɛ4 allele. The extent severity neuronal loss cases. Analysis revealed more premature plaques α-Synuclein amplification showed differences kinetics two This study highlights rare variant which there anatomical meeting point α-synuclein, i.e. striatum cerebellum. Since biomarkers entering practice, will recognized, clinicians have informed that prognosis necessarily than pure but effect potential α-synuclein-based therapies might influenced by co-presence regions where also aggregates. propose should interpreted only based on phenotype whether protein depositions regionally overlap, potentially leading response α-synuclein-targeted therapies.

Язык: Английский

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Unlocking the Potential: Semaglutide’s Impact on Alzheimer’s and Parkinson’s Disease in Animal Models

Current Issues in Molecular Biology, Год журнала: 2024, Номер 46(6), С. 5929 - 5949

Опубликована: Июнь 13, 2024

Semaglutide (SEM), a glucagon-like peptide-1 receptor agonist, has garnered increasing interest for its potential therapeutic effects in neurodegenerative disorders such as Alzheimer’s disease (AD) and Parkinson’s (PD). This review provides comprehensive description of SEM’s mechanism action preclinical studies these debilitating conditions. In animal models AD, SEM proved beneficial on multiple pathological hallmarks the disease. administration been associated with reductions amyloid-beta plaque deposition mitigation neuroinflammation. Moreover, treatment shown to ameliorate behavioral deficits related anxiety social interaction. SEM-treated animals exhibit improvements spatial learning memory retention tasks, evidenced by enhanced performance maze navigation tests novel object recognition assays. Similarly, PD, demonstrated promising neuroprotective through various mechanisms. These include modulation neuroinflammation, enhancement mitochondrial function, promotion neurogenesis. Additionally, improve motor function dopaminergic neuronal loss, offering disease-modifying strategies. Overall, accumulating evidence from suggests that holds promise approach AD PD. Further research is warranted elucidate underlying mechanisms translate findings into clinical applications devastating disorders.

Язык: Английский

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Cerebrospinal fluid lipidomic fingerprint of obstructive sleep apnoea in Alzheimer’s disease

Alzheimer s Research & Therapy, Год журнала: 2023, Номер 15(1)

Опубликована: Авг. 7, 2023

Abstract Background Obstructive sleep apnoea (OSA) has a high prevalence in patients with Alzheimer’s disease (AD). Both conditions have been shown to be associated lipid dysregulation. However, the relationship between OSA severity and alterations metabolism brains of AD yet fully elucidated. In this context, we examined cerebrospinal fluid (CSF) lipidome suspected identify potential diagnostic biomarkers provide insights into pathophysiological mechanisms underlying effect on AD. Methods The study included 91 consecutive who underwent overnight polysomnography (PSG) diagnose severe (apnoea-hypopnea index ≥ 30/h). next morning, CSF samples were collected analysed by liquid chromatography coupled mass spectrometry an LC-ESI-QTOF-MS/MS platform. Results levels 11 species significantly different ( N = 38) without 58) OSA. Five lipids (including oxidized triglyceride OxTG(57:2) four unknown lipids) correlated specific PSG measures related fragmentation hypoxemia. Our analyses revealed 4-lipid signature ceramide OxCer(40:6) three that provided accuracy 0.80 (95% CI: 0.71–0.89) detection These increased discriminative power STOP-Bang questionnaire terms area under curve (AUC) from 0.61 (0.50–0.74) 0.85 (0.71–0.93). Conclusions results reveal lipidomic fingerprint allows identification findings suggest increase central nervous system lipoxidation may principal mechanism association

Язык: Английский

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The Synergistic Potential of Combining PD-1/PD-L1 Immune Checkpoint Inhibitors with NOD2 Agonists in Alzheimer’s Disease Treatment

International Journal of Molecular Sciences, Год журнала: 2023, Номер 24(13), С. 10905 - 10905

Опубликована: Июнь 30, 2023

Our research over the past decade has compellingly demonstrated potential of Nucleotide-binding oligomerization domain-containing protein 2 (NOD2) receptor agonists in Alzheimer’s disease (AD) treatment. These facilitate conversation pro-inflammatory monocytes into patrolling monocytes, leading to efficient clearance amyloid-β (Aβ) AD-affected cerebrovascular system. This approach surpasses efficacy targeting Aβ formation, marking a significant shift therapeutic strategies. Simultaneously, inhibitors PD-1/PD-L1 immune check point or glycogen synthase kinase 3 beta (GSK3β), which modulates PD-1, have emerged as potent AD treatment modalities. PD-1 inhibitor exhibits profound monocytes’ recruitment AD-afflicted brain. Recent evidence suggests that an integrated approach, combining modulation NOD2 and could yield superior outcomes. innovative combinatorial leverages MDP act catalyst for conversion inflammatory with subsequent these brain being stimulated by inhibitor. interventions are currently under preclinical investigation pharmaceutical entities, underscoring promise they hold. advocates modulation, rather than suppression, innate system promising pharmacological strategy AD.

Язык: Английский

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The shift in the fatty acid composition of the circulating lipidome in Alzheimer's disease

Alzheimer s & Dementia, Год журнала: 2024, Номер 20(5), С. 3322 - 3333

Опубликована: Март 27, 2024

Fatty acids (FAs) are the building blocks of complex lipids and signaling compounds; role lipidome fatty acid profile (LFA) in AD progression remains unclear.

Язык: Английский

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