Modern approaches to investigating non‐neuronal aspects of Alzheimer's disease

Liddelow, Shane A.

doi:10.1096/fj.201802592

Cited by 18 publications

(10 citation statements)

References 61 publications

(94 reference statements)

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“…The potential role of glia in neurodegenerative disease has been discussed for some decades now (Itagaki et al 1989;Henstridge et al 2019). However, such studies have largely focussed on abnormal glia behavior such as activation of microglia or the formation of astrocyte scars and the secretion of pro-inflammatory cytokines (Liddelow 2019). However, there is increasing evidence that glia cells undergo an aging process and this may also impact neurodegenerative disease progression (Spittau 2017;Holtzman and Ulrich 2019;Cohen and Torres 2019).…”

mentioning

confidence: 99%

Microglia and the aging brain: are senescent microglia the key to neurodegeneration?

Angelova

Brown

2019

Journal of Neurochemistry

195

125

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The single largest risk factor for etiology of neurodegenerative diseases like Alzheimer’s disease is increased age. Therefore, understanding the changes that occur as a result of aging is central to any possible prevention or cure for such conditions. Microglia, the resident brain glial population most associated with both protection of neurons in health and their destruction is disease, could be a significant player in age related changes. Microglia can adopt an aberrant phenotype sometimes referred to either as dystrophic or senescent. While aged microglia have been frequently identified in neurodegenerative diseases such as Alzheimer’s disease, there is no conclusive evidence that proves a causal role. This has been hampered by a lack of models of aged microglia. We have recently generated a model of senescent microglia based on the observation that all dystrophic microglia show iron overload. Iron‐overloading cultured microglia causes them to take on a senescent phenotype and can cause changes in models of neurodegeneration similar to those observed in patients. This review considers how this model could be used to determine the role of senescent microglia in neurodegenerative diseases.

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mentioning

confidence: 99%

Microglia and the aging brain: are senescent microglia the key to neurodegeneration?

Angelova

Brown

2019

Journal of Neurochemistry

195

125

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“…It is not properly a marker of inflammation, but it is a sign of a reactive brain milieu, as astrocytes tend to proliferate in response to tissue injury, and eventually release large amounts of GFAP in the interstitial fluid. Recently, the astrocytic response to brain damage and the inflammatory microglia has been characterized [297][298][299], and is very relevant in the context of AD pathology. The currently available CSF GFAP data show a correlation between increased levels and Aβ and tau evidence of AD [115,300], and recent data on plasma GFAP showed increased concentrations in late and early onset AD patients compared with cognitively normal controls [301].…”

Section: Other Biomarkers Of Inflammation and Glial Activationmentioning

confidence: 99%

Significance of Blood and Cerebrospinal Fluid Biomarkers for Alzheimer’s Disease: Sensitivity, Specificity and Potential for Clinical Use

d’Abramo

D’Adamio

Giliberto

2020

JPM

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Alzheimer’s disease (AD) is the most common type of dementia, affecting more than 5 million Americans, with steadily increasing mortality and incredible socio-economic burden. Not only have therapeutic efforts so far failed to reach significant efficacy, but the real pathogenesis of the disease is still obscure. The current theories are based on pathological findings of amyloid plaques and tau neurofibrillary tangles that accumulate in the brain parenchyma of affected patients. These findings have defined, together with the extensive neurodegeneration, the diagnostic criteria of the disease. The ability to detect changes in the levels of amyloid and tau in cerebrospinal fluid (CSF) first, and more recently in blood, has allowed us to use these biomarkers for the specific in-vivo diagnosis of AD in humans. Furthermore, other pathological elements of AD, such as the loss of neurons, inflammation and metabolic derangement, have translated to the definition of other CSF and blood biomarkers, which are not specific of the disease but, when combined with amyloid and tau, correlate with the progression from mild cognitive impairment to AD dementia, or identify patients who will develop AD pathology. In this review, we discuss the role of current and hypothetical biomarkers of Alzheimer’s disease, their specificity, and the caveats of current high-sensitivity platforms for their peripheral detection.

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“…One of the key characteristics of AD is the substantial and progressive erosion of neurons in the cortex [57]. Indeed, maximal degeneration takes place in the cortex and hippocampus, which leads to de iciencies in both learning and memory [58]. Typically, AD symptoms commence with mild amnesia and confusion, eventually leading to radical changes in the personality of the af licted individual [59].…”

Section: Alzheimer's Disease (Ad)mentioning

confidence: 99%

Protection from the Pathogenesis of Neurodegenerative Disorders, including Alzheimer’s Disease, Amyotrophic Lateral Sclerosis, Huntington’s Disease, and Parkinson’s Diseases, through the Mitigation of Reactive Oxygen Species

Madireddy¹,

Madireddy²

2019

J Neurosci Neurol Disord

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Vitamin E Antioxidant, Neuroprotection Vitamin E is a scavenger of several ROS and serves to reduce their reactivity and toxicity. It offers protection from the propagative damage of ROS by inhibiting the oxidative modifi cation of lipoproteins AD [74-79,82-86] PD [175-177,79] ALS [193,217,218] Vitamin C Antioxidant, Neuroprotection Vitamin C is an excellent antioxidant, suitable in reducing ROS levels, lipid peroxidation, and oxidative stress. It is also useful in regenerating other antioxidants. AD [81,82,75,77,79] PD [166-168] ALS [213,214] Vitamin D Antioxidant Neuroprotection Vitamin D prevent oxidative stress, lower the production of free radicals, and reduce neurotoxicity through the enhancement of autophagy signaling pathways AD [74-78,30,16,80] PD [157-159,169-174] ALS [215,216] Vitamin A Antioxidan Vitamin A prevent the formation of Aβ plaques AD [16,30,74-78] Vitamin B Antioxidant Neuroprotection Vitamin B perform antioxidant and neuroprotective functions AD [88-90] PD [157-159,162-165] HD [105] Curcumin Antioxidant Anti-infl ammatory Neuroprotection Curcumin is a scavenger of free radicals and reduces mitochondrial disfunction. AD [100,101] Omega−3 fatty acids Antioxidant Anti-infl ammatory Omega-3 fatty acids reduce ROS formation acting as free radical scavengers.

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Modern approaches to investigating non‐neuronal aspects of Alzheimer's disease

Cited by 18 publications

References 61 publications

Microglia and the aging brain: are senescent microglia the key to neurodegeneration?

Microglia and the aging brain: are senescent microglia the key to neurodegeneration?

Significance of Blood and Cerebrospinal Fluid Biomarkers for Alzheimer’s Disease: Sensitivity, Specificity and Potential for Clinical Use

Protection from the Pathogenesis of Neurodegenerative Disorders, including Alzheimer’s Disease, Amyotrophic Lateral Sclerosis, Huntington’s Disease, and Parkinson’s Diseases, through the Mitigation of Reactive Oxygen Species

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