Alterations in mitochondrial number and function in Alzheimer’s disease fibroblasts

Background: Utilities of blood-based biomarkers in Alzheimer’s disease (AD) clinical trials remain unknown. Objective: To evaluate the ability of plasma neurofilament light chain (NfL) to predict future declines in cognition and activities of daily living (ADL) outcomes in 26 older adults with mild-to-moderate AD dementia from the FIT-AD Trial. Methods: Plasma NfL was measured at baseline and 3 and 6 months. Cognition and ADL were assessed using the AD Assessment Scale-Cognition (ADAS-Cog) and AD Uniform Dataset Instruments and Disability Assessment for Dementia (DAD), respectively, at baseline, 3, 6, 9, and 12 months. Linear mixed effects models were used to examine the associations between baseline or change in plasma NfL and changes in outcomes. Results: Higher baseline plasma NfL was associated with greater rate of decline in ADAS-Cog from baseline to 6 months (standardized estimate of 0.00462, p = 0.02853) and in ADL from baseline to 12 months (standardized estimate of –0.00284, p = 0.03338). Greater increase in plasma NfL in short term from baseline to 3 months was associated with greater rate of decline in memory and ADL from 3 to 6 months (standardized estimate of –0.04638 [0.003], p = 0.01635; standardized estimate of –0.03818, p = 0.0435) and greater rate of decline in ADL from 3 to 12 month (standardized estimate of –0.01492, p = 0.01082). Conclusion: This study demonstrated that plasma NfL might have the potential to predict cognitive and function decline up to 12 months. However, future studies with bigger sample sizes need to confirm the findings.

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Microglial Function and Regulation during Development, Homeostasis and Alzheimer’s Disease

Cells ◽

10.3390/cells10040957 ◽

2021 ◽

Vol 10 (4) ◽

pp. 957

Author(s):

Brad T. Casali ◽

Erin G. Reed-Geaghan

Keyword(s):

Alzheimer’S Disease ◽

Alzheimer's Disease ◽

Immune Cells ◽

Expression Patterns ◽

Brain Parenchyma ◽

Primary Role ◽

And Function ◽

Inflammatory Milieu ◽

The Brain ◽

Homeostatic State

Microglia are the resident immune cells of the brain, deriving from yolk sac progenitors that populate the brain parenchyma during development. During development and homeostasis, microglia play critical roles in synaptogenesis and synaptic plasticity, in addition to their primary role as immune sentinels. In aging and neurodegenerative diseases generally, and Alzheimer’s disease (AD) specifically, microglial function is altered in ways that significantly diverge from their homeostatic state, inducing a more detrimental inflammatory environment. In this review, we discuss the receptors, signaling, regulation and gene expression patterns of microglia that mediate their phenotype and function contributing to the inflammatory milieu of the AD brain, as well as strategies that target microglia to ameliorate the onset, progression and symptoms of AD.

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Astrocytic transporters in Alzheimer's disease

Biochemical Journal ◽

10.1042/bcj20160505 ◽

2017 ◽

Vol 474 (3) ◽

pp. 333-355 ◽

Cited By ~ 7

Author(s):

Chris Ugbode ◽

Yuhan Hu ◽

Benjamin Whalley ◽

Chris Peers ◽

Marcus Rattray ◽

...

Keyword(s):

Alzheimer’S Disease ◽

Alzheimer's Disease ◽

Early Stage ◽

Neurological Diseases ◽

Current Evidence ◽

Specific Targeting ◽

Disease Modifying Therapies ◽

The Central Nervous System ◽

Disease Modifying ◽

And Function

Astrocytes play a fundamental role in maintaining the health and function of the central nervous system. Increasing evidence indicates that astrocytes undergo both cellular and molecular changes at an early stage in neurological diseases, including Alzheimer's disease (AD). These changes may reflect a change from a neuroprotective to a neurotoxic phenotype. Given the lack of current disease-modifying therapies for AD, astrocytes have become an interesting and viable target for therapeutic intervention. The astrocyte transport system covers a diverse array of proteins involved in metabolic support, neurotransmission and synaptic architecture. Therefore, specific targeting of individual transporter families has the potential to suppress neurodegeneration, a characteristic hallmark of AD. A small number of the 400 transporter superfamilies are expressed in astrocytes, with evidence highlighting a fraction of these are implicated in AD. Here, we review the current evidence for six astrocytic transporter subfamilies involved in AD, as reported in both animal and human studies. This review confirms that astrocytes are indeed a viable target, highlights the complexities of studying astrocytes and provides future directives to exploit the potential of astrocytes in tackling AD.

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Microglia-Based Sex-Biased Neuropathology in Early-Stage Alzheimer’s Disease Model Mice and the Potential Pharmacologic Efficacy of Dioscin

Cells ◽

10.3390/cells10113261 ◽

2021 ◽

Vol 10 (11) ◽

pp. 3261

Author(s):

Xiao Liu ◽

Qian Zhou ◽

Jia-He Zhang ◽

Xiaoying Wang ◽

Xiumei Gao ◽

...

Keyword(s):

Alzheimer’S Disease ◽

Alzheimer's Disease ◽

Early Stage ◽

Disease Model ◽

Amyloid Β ◽

Brain Lesions ◽

Synaptic Dysfunction ◽

Synaptic Loss ◽

And Function ◽

The Brain

Alzheimer’s disease (AD), the most common form of dementia, is characterized by amyloid-β (Aβ) accumulation, microglia-associated neuroinflammation, and synaptic loss. The detailed neuropathologic characteristics in early-stage AD, however, are largely unclear. We evaluated the pathologic brain alterations in young adult App knock-in model AppNL-G-F mice at 3 and 6 months of age, which corresponds to early-stage AD. At 3 months of age, microglia expression in the cortex and hippocampus was significantly decreased. By the age of 6 months, the number and function of the microglia increased, accompanied by progressive amyloid-β deposition, synaptic dysfunction, neuroinflammation, and dysregulation of β-catenin and NF-κB signaling pathways. The neuropathologic changes were more severe in female mice than in male mice. Oral administration of dioscin, a natural product, ameliorated the neuropathologic alterations in young AppNL-G-F mice. Our findings revealed microglia-based sex-differential neuropathologic changes in a mouse model of early-stage AD and therapeutic efficacy of dioscin on the brain lesions. Dioscin may represent a potential treatment for AD.

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Mesenchymal Stem Cell-Derived Extracellular Vesicle-Based Therapy for Alzheimer’s Disease: Progress and Opportunity

Membranes ◽

10.3390/membranes11100796 ◽

2021 ◽

Vol 11 (10) ◽

pp. 796

Author(s):

Yi-An Chen ◽

Cheng-Hsiu Lu ◽

Chien-Chih Ke ◽

Ren-Shyan Liu

Keyword(s):

Alzheimer’S Disease ◽

Alzheimer's Disease ◽

Neurodegenerative Disorder ◽

Therapeutic Potential ◽

Extracellular Vesicle ◽

Synaptic Loss ◽

Molecular Machinery ◽

And Function ◽

Preclinical And Clinical Studies ◽

Ad Therapy

Alzheimer’s disease (AD), as a neurodegenerative disorder, is characterized by mass neuronal and synaptic loss and, currently, there are no successful curative therapies. Extracellular vesicles (EVs) are an emerging approach to intercellular communication via transferring cellular materials such as proteins, lipids, mRNAs, and miRNAs from parental cells to recipient cells, leading to the reprogramming of the molecular machinery. Numerous studies have suggested the therapeutic potential of EVs derived from mesenchymal stem cells (MSCs) in the treatment of AD, based on the neuroprotective, regenerative and immunomodulatory effects as effective as MSCs. In this review, we focus on the biology and function of EVs, the potential of MSC-derived EVs for AD therapy in preclinical and clinical studies, as well as the potent mechanisms of MSC-derived EVs actions. Finally, we highlight the modification strategies and diagnosis utilities in order to make advance in this field.

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Sex Differences and the Influence of Sex Hormones on Cognition through Adulthood and the Aging Process

Brain Sciences ◽

10.3390/brainsci8090163 ◽

2018 ◽

Vol 8 (9) ◽

pp. 163 ◽

Cited By ~ 17

Author(s):

Caroline Gurvich ◽

Kate Hoy ◽

Natalie Thomas ◽

Jayashri Kulkarni

Keyword(s):

Alzheimer’S Disease ◽

Alzheimer's Disease ◽

Sex Differences ◽

Cognitive Functioning ◽

Sex Hormones ◽

Reproductive Function ◽

Health And Disease ◽

And Function ◽

The Brain

Hormones of the hypothalamic-pituitary-gonadal (HPG) axis that regulate reproductive function have multiple effects on the development, maintenance and function of the brain. Sex differences in cognitive functioning have been reported in both health and disease, which may be partly attributed to sex hormones. The aim of the current paper was to provide a theoretical review of how sex hormones influence cognitive functioning across the lifespan as well as provide an overview of the literature on sex differences and the role of sex hormones in cognitive decline, specifically in relation to Alzheimer’s disease (AD). A summary of current hormone and sex-based interventions for enhancing cognitive functioning and/or reducing the risk of Alzheimer’s disease is also provided.

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THE BIOLOGICAL ACTIVITIES AND FUNCTION OF THE AMYLOID PRECURSOR PROTEIN OF ALZHEIMER’S DISEASE

MOLECULAR BIOLOGY OF ALZHEIMER’S DISEASE ◽

10.4324/9780203303610_chapter_4 ◽

2010 ◽

Author(s):

GERD MULTHAUP ◽

COLIN L MASTERS ◽

KONRAD BEYREUTHER ◽

ROBERTO CAPPAI

Keyword(s):

Alzheimer’S Disease ◽

Alzheimer's Disease ◽

Amyloid Precursor Protein ◽

Biological Activities ◽

Precursor Protein ◽

And Function

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Neuroimaging Approaches for Elderly Studies

Medical Imaging ◽

10.4018/978-1-5225-0571-6.ch067 ◽

2017 ◽

pp. 1576-1617

Author(s):

Charis Styliadis ◽

Panagiotis Kartsidis ◽

Evangelos Paraskevopoulos

Keyword(s):

Alzheimer’S Disease ◽

Alzheimer's Disease ◽

Structure And Function ◽

Cognitive Capacity ◽

Aging Brain ◽

Cerebral Structure ◽

Age Related ◽

Elderly Populations ◽

And Function ◽

Age Related Changes

Advances in the field of neuroimaging have allowed for the examination of the effects of age-related changes on cognitive capacity in elderly populations. Structural techniques are now routinely used to report cortical atrophic rates in aging and particularly within the context of the Alzheimer's disease, and may be integrated with functional techniques which examine the functional characteristics of the cortex at rest and during the performance of a task. Despite advancing age cognitive function remains highly plastic, allowing for interventions that aim to maintain or even remediate its capacity and the mechanisms by which structure and function are altered among seniors. Overall, information on the integrity of the cerebral structure and function aid in the early detection and treatment of the Alzheimer's disease as well as the evaluation and track of the disease's progression. In this chapter, neuroimaging methods are presented along with findings that are particularly relevant for the study of neuroplasticity in the aging brain.

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