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Dementia
Published in Henry J. Woodford, Essential Geriatrics, 2022
FTD has several variants, including Pick disease. This latter condition is distinguished pathologically by the presence of Pick bodies, which are argentophilic intracellular inclusions. Tau protein is a normal cellular component of microtubules. FTD is associated with abnormal processing of this protein, often with hyperphosphorylation. Other conditions associated with tau abnormalities include PSP and corticobasal degeneration (CBD) (see page 188 and page 189) – together termed ‘tauopathies'. As suggested by the name, FTD predominantly affects the frontal and anterior temporal lobes. It is a more common cause of younger-onset dementia and uncommonly presents after age 65.50
Role of Vitamin D and Antioxidant Functional Foods in the Prevention and Treatment of Alzheimer’s Disease Pathology
Published in Abhai Kumar, Debasis Bagchi, Antioxidants and Functional Foods for Neurodegenerative Disorders, 2021
Secondary accumulation of tau protein has also been considered a determinant factor in AD progression. Beta-amyloid induces increased tau phosphorylation and translocation to the cytoplasm, which are associated with neurodegeneration. Cerebrospinal fluid (CSF) phosphorylated tau (P-tau) and cortical tau are considered disease biomarkers (Jack et al., 2018). The primary biological function of tau may be directly associated with microtubule stabilization (Kneynsberg, Combs, Christensen, Morfini, & Kanaan, 2017). Tau binds microtubules and hyperphosphorylation causes aberrant aggregation to the cytoskeletal proteins, which, in turn, cause axonal transport malfunction (Sanabria-Castro et al., 2017). Hyperphosphorylation also causes a change in the conformation of tau leading to the disassembly of the microtubule and formation of paired helical filaments, which then cause aggregation and formation of NFT. Once affected, tau spreads through the brain, via transcellular spreading, and can induce synaptotoxicity (Demaegd, Schymkowitz, & Rousseau, 2018). Axonal pathology is a common outcome of many human tauopathies. In AD, axonal demyelination/dystrophy can occur in the prodromal disease stage that progresses from the cortex into the corpus callosum and has a direct correlation with cognitive decline (Kneynsberg et al., 2017).
Pea
Published in Sahar Swidan, Matthew Bennett, Advanced Therapeutics in Pain Medicine, 2020
Alzheimer disease (AD) is characterized by beta amyloid plaques, gliosis, and tau protein hyperphosphorylation leading to cognitive deficits in those affected. In an animal study by Scuderi et al.,20 beta amyloid was administered to the hippocampus of rats followed by PEA and the PPAR-α antagonist GW6471. The investigators found that PEA administration was correlated with a reduction in amnestic and cognitive deficits in the AD model rats. These results show a possible therapeutic option for AD patients for the improvement in cognitive deficits as well as disease progression.
A review of potential neuropathological changes associated with ketamine
Published in Expert Opinion on Drug Safety, 2022
Danica Nogo, Hana Nazal, Yuetong Song, Kayla M. Teopiz, Roger Ho, Roger S. McIntyre, Leanna M.W. Lui, Joshua D. Rosenblat
Two studies operating under chronic ketamine exposure both showed significant increases in tau hyperphosphorylation [62,63]. One study showed increases in the prefrontal and entorhinal cortices of monkeys and the prefrontal cortex of mice following chronic ketamine administration (1 mg/kg for 6 months and 30 mg/kg for 1, 3, or 6 months, respectively) [63], whereas the other study showed increases in the hippocampus of mice following ketamine injections (30 or 60 mg/kg for 6 months) [62]. Moreover, increased levels of tau hyperphosphorylation were reported at serine residues 202 and 296 and threonine residue 205 [62]. A separate study, analyzing changes in tau hyperphosphorylation levels using immunohistochemical and immunofluorescence assays, showed significantly increased immunoreactivity levels and intensity of tau staining [62]. Immunohistochemical staining was mainly distributed in the perikaryal and neurite regions of the hippocampus, and immunofluorescence staining was concentrated in the pyramidal cell layer of the CA3 region of the hippocampus [62].
Impact of Alzheimer’s Disease in Ocular Motility and Visual Perception: A Narrative Review
Published in Seminars in Ophthalmology, 2022
Alzheimer’s disease (AD) is a neurodegenerative disease with multiple etiologies.1In this disease, there is a progressive neuronal loss and an accumulation of amyloid-ß (Åß) peptides, causing the nervous system to be unable to perform its function normally.1It is the most common form of dementia (50%–70%),2,3 and affects around 10% of the population aged over 65, a percentage that can rise over the next few decades. According to the World Health Organization (WHO), in 2050, AD will affect 150 million people, impacting the quality of life of our senior citizens. In industrialized countries, it will rise sharply due to the ageing of the population mass, although it should not be considered as a normal part of ageing.2 The cost associated with AD and other dementias is equivalent to 1% of global gross domestic product (GDP).4 One of its most common symptoms is the loss of the most recent events, preserving for longer time memories of more remote times, such as youth or childhood.5,6 Clinically, AD is characterized by cognitive and social impairment (the most common behavioral changes are apathy and disconnection)7 and pathologically by the accumulation of amyloid-ß neuronal plaques and the hyperphosphorylation of TAU, compromising the formation of neurofibrillary tangles in the brain.1,3 Amyloid-ß deposition is associated with transverse synaptic network dysfunction, progressive cerebral atrophy, and longitudinal cognitive deterioration. Hyperphosphorylation of TAU is observed in advanced stages of the disease.1,3
TDZD-8 alleviates delayed neurological sequelae following acute carbon monoxide poisoning involving tau protein phosphorylation
Published in Inhalation Toxicology, 2020
Chenglei Su, Ningjun Zhao, Jianjiao Zou, Xianliang Yan
GSK-3β is thought play a critical role in Tau phosphorylation (Dey et al. 2017). The hyperphosphorylation of Tau is considered to impair cognitive function (Wang and Mandelkow 2016), as phosphorylation is increased in many neurodegenerative diseases, such as AD or ischemic neurological deficit (Mukrasch et al. 2009; Pluta et al. 2018). Hyperphosphorylation of Tau might induce synaptic dysfunction (Thies and Mandelkow 2007; Hoover et al. 2010) and enhance tau aggregation. What’s more, hyperphosphorylation of tau might lead to abnormal accumulation of F-actin filaments (Fulga et al. 2007) and impairment of kinesin complex (Fulga et al. 2007). Our results confirmed that the protein level of phosphorylation of Tau significantly increased in rat brain after CO exposure. TDZD-8 treatment decreased the hyperphosphorylation of Tau induced by CO poisoning. It is suggested that Tau was involved in the mechanisms of TDZD-8 neuroprotection.