IL-1β and TNF-α play an important role in modulating the risk of periodontitis and Alzheimer’s disease

Journal of Neuroinflammation, Journal Year: 2023, Volume and Issue: 20(1)

Published: March 13, 2023

Systemic activation of the immune system can exert detrimental effects on central nervous system. Periodontitis, a chronic disease oral cavity, is common source systemic inflammation. Neuroinflammation might be result this to accelerate progressive deterioration neuronal functions during aging or exacerbate pre-existing neurodegenerative diseases, such as Alzheimer's disease. With advancing age, increase in body's pro-inflammatory status favors state vulnerability both periodontitis and In present study, we sought delineate roles cytokines pathogenesis diseases.To examine impacts onset progression disease, 6-month-old female 3 × Tg-AD mice their age-matched non-transgenic were employed. Periodontitis was induced using two different experimental models: heat-killed bacterial-induced ligature-induced periodontitis. To interleukin 1 beta (IL-1β) tumor necrosis factor-alpha (TNF-α) also injected into buccal mandibular vestibule mice.Here, show that IL-1β TNF-α most important earliest upregulated upon periodontal infection. The upregulation these promoted environment brain contributing development disease-like pathology cognitive dysfunctions. Periodontitis-induced inflammation enhanced inflammatory responses subsequently exacerbated impairment mice. role connecting further affirmed conventional magnetization transfer experiment which increased glial resulting from led decreased ratios mice.Systemic contributed tau decline It potentiated pathological features function Taken together, study provides convincing evidence serves link between

Language: Английский

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Neurobehavioral meaning of pupil size

Neuron, Journal Year: 2024, Volume and Issue: 112(20), P. 3381 - 3395

Published: June 25, 2024

Pupil size is a widely used metric of brain state. It one the few signals originating from that can be readily monitored with low-cost devices in basic science, clinical, and home settings. is, therefore, important to investigate generate well-defined theories related specific interpretations this metric. What exactly does it tell us about brain? Pupils constrict response light dilate during darkness, but also controls pupil irrespective luminosity. fluctuations resulting ongoing "brain states" are as arousal, what pupil-linked arousal how should interpreted neural, cognitive, computational terms? Here, we discuss some recent findings these issues. We identify open questions propose answer them through combination tasks, neurocomputational models, neurophysiological probing interconnected loops causes consequences size.

Language: Английский

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Spatiotemporal patterns of locus coeruleus integrity predict cortical tau and cognition

Nature Aging, Journal Year: 2024, Volume and Issue: 4(5), P. 625 - 637

Published: April 25, 2024

Abstract Autopsy studies indicated that the locus coeruleus (LC) accumulates hyperphosphorylated tau before allocortical regions in Alzheimer’s disease. By combining vivo longitudinal magnetic resonance imaging measures of LC integrity, positron emission tomography and cognition with autopsy data transcriptomic information, we examined whether changes precede deposition specific genetic features underlie LC’s selective vulnerability to tau. We found integrity preceded medial temporal lobe accumulation, together these processes were associated lower cognitive performance. Common gene expression profiles between LC–medial lobe–limbic map biological functions protein transport regulation. These findings advance our understanding spatiotemporal patterns initial spreading from disease pathology. can be a promising indicator for identifying time window when individuals are at risk progression underscore importance interventions mitigating spread.

Language: Английский

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In vivo visualization of age-related differences in the locus coeruleus

Neurobiology of Aging, Journal Year: 2018, Volume and Issue: 74, P. 101 - 111

Published: Oct. 20, 2018

The locus coeruleus (LC), the major origin of noradrenergic modulation central nervous system, may play an important role in neuropsychiatric disorders including Parkinson's disease and Alzheimer's disease. pattern age-related change LC across life span is unclear. We obtained normalized, mean signal intensity values, that is, contrast ratios (CRs), from magnetization transfer-weighted images to investigate relationship between CR age cognitively normal healthy adults (N = 605, range 18-88 years). Study participants were part Cambridge Centre for Ageing Neuroscience-an open-access, population-based data set. found a quadratic age, peak occurring around 60 years, with no differences males females. Subregional analyses revealed decline was confined rostral portion LC. Older showed greater variance overall than younger adults, functional clinical implications these observed require further investigation. Visualization this study inform how future scanning parameters can be optimized, provides insight into integrity changes span.

Language: Английский

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Revisiting the intersection of amyloid, pathologically modified tau and iron in Alzheimer’s disease from a ferroptosis perspective

Progress in Neurobiology, Journal Year: 2019, Volume and Issue: 184, P. 101716 - 101716

Published: Oct. 8, 2019

Language: Английский

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Locus Coeruleus Ablation Exacerbates Cognitive Deficits, Neuropathology, and Lethality in P301S Tau Transgenic Mice

Journal of Neuroscience, Journal Year: 2017, Volume and Issue: 38(1), P. 74 - 92

Published: Nov. 13, 2017

The brainstem locus coeruleus (LC) supplies norepinephrine to the forebrain and degenerates in Alzheimer's disease (AD). Loss of LC neurons is correlated with increased severity other AD hallmarks, including β-amyloid (Aβ) plaques, tau neurofibrillary tangles, cognitive deficits, suggesting that it contributes progression. Lesions amyloid-based transgenic mouse models exacerbate Aβ pathology, neuroinflammation, but unknown how loss affects tau-mediated pathology or behavioral abnormalities. Here we investigate impact degeneration a model tauopathy by lesioning male female P301S mice neurotoxin N-(2-chloroethyl) -N- ethyl-bromobenzylamine (DSP-4) starting at 2 months age. By 6 months, deficits hippocampal-dependent spatial (Morris water maze) associative (contextual fear conditioning) memory were observed lesioned while performance remained intact all genotype treatment groups, indicating act synergistically impair cognition. 10 hippocampal neuroinflammation neurodegeneration typically unlesioned exacerbated DSP-4, mortality was also accelerated. These DSP-4-induced changes accompanied only mild aggravation burden cannot fully account for effects degeneration. Combined, these experiments demonstrate noradrenergic exacerbates multiple phenotypes caused pathogenic tau, provides complementary data highlight dual role has on both pathologies AD. SIGNIFICANCE STATEMENT Elucidating mechanisms underlying crucial developing effective diagnostics therapeutics. transmission have been recognized as ubiquitous events previous studies demonstrated lesions models. Here, reveal aspects using selective system an exacerbation tauopathy. Our support integral modulating canonical AD-associated pathologies, well detrimental consequences during

Language: Английский

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Age-dependent behavioral and biochemical characterization of single APP knock-in mouse (APPNL-G-F/NL-G-F) model of Alzheimer's disease

Neurobiology of Aging, Journal Year: 2018, Volume and Issue: 75, P. 25 - 37

Published: Nov. 5, 2018

Language: Английский

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Biomarkers for Alzheimer’s Disease Early Diagnosis

Journal of Personalized Medicine, Journal Year: 2020, Volume and Issue: 10(3), P. 114 - 114

Published: Sept. 4, 2020

Alzheimer's disease (AD) is the most common cause of dementia, affecting central nervous system (CNS) through accumulation intraneuronal neurofibrillary tau tangles (NFTs) and β-amyloid plaques. By time AD clinically diagnosed, neuronal loss has already occurred in many brain retinal regions. Therefore, availability early reliable diagnosis markers would allow its detection taking preventive measures to avoid loss. Current diagnostic tools brain, such as magnetic resonance imaging (MRI), positron emission tomography (PET) imaging, cerebrospinal fluid (CSF) biomarkers (Aβ tau) are invasive expensive. Brain-secreted extracellular vesicles (BEVs) isolated from peripheral blood have emerged novel strategies study AD, with enormous potential a evaluation therapeutics treatment tools. In addition; similar mechanisms neurodegeneration been demonstrated eyes patients. Since more accessible than several eye tests that detect cellular vascular changes retina also proposed screening biomarkers. The aim this summarize discuss eye, blood, other biofluids like saliva urine, correlate them earlier prognosis identify individuals mild symptoms prior dementia.

Language: Английский

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The basis of cellular and regional vulnerability in Alzheimer’s disease

Acta Neuropathologica, Journal Year: 2019, Volume and Issue: 138(5), P. 729 - 749

Published: Aug. 7, 2019

Language: Английский

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Systems-based proteomics to resolve the biology of Alzheimer’s disease beyond amyloid and tau

Neuropsychopharmacology, Journal Year: 2020, Volume and Issue: 46(1), P. 98 - 115

Published: Sept. 8, 2020

Abstract The repeated failures of amyloid-targeting therapies have challenged our narrow understanding Alzheimer’s disease (AD) pathogenesis and inspired wide-ranging investigations into the underlying mechanisms disease. Increasing evidence indicates that AD develops from an intricate web biochemical cellular processes extend far beyond amyloid tau accumulation. This growing recognition surrounding diversity pathophysiology underscores need for holistic systems-based approaches to explore pathogenesis. Here we describe how network-based proteomics has emerged as a powerful tool its application brain provided informative framework complex protein Furthermore, outline network proteome can be leveraged advance additional scientific translational efforts, including discovery novel biomarkers

Language: Английский

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