Genetic, Biochemical and Histopathological Aspects of Familiar Alzheimer's Disease

Ortíz, Genaro Gabriel; Pacheco-Moisés, Fermín Paul; Renovato, Erika D. González; Figuera, Luis E.; Macías-Islas, Miguel Ángel; Ramírez, Mario Mireles; Flores-Alvarado, Luis Javier; Sánchez-López, Angélica Lizeth; G.Nuño-Penilla, Dhea; Brizuela, Irma E. Velázquez; Sánchez-Luna, Juan Pablo; Rosa, Alfredo Celis de la

doi:10.5772/59809

Cited by 8 publications

(19 citation statements)

References 118 publications

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“…Besides lipid metabolism, ApoE ε4 polymorphism has been related to an alteration of Aβ levels, oxidative status, and membrane’s composition, even before the onset of AD [8,9]. In this sense, nowadays, the study of the cellular and molecular pathways which lead to AD [42], and the investigation of AD prognostic markers, are wide themes of research [43].…”

Section: Discussionmentioning

confidence: 99%

“…The alteration of membrane fluidity is a consequence of high oxidative stress and modification in membrane phospholipids amount, which occurs in aging [36] and characterizes some diseases, including AD [9]. Herein, ApoE ε4 carriers displayed lower levels of membrane fluidity than non-ε4 subjects.…”

Section: Discussionmentioning

confidence: 99%

“…In particular, elevated oxidative damage in ε4 homozygotes has been linked to increased levels of lipid peroxidation [7], causing an alteration in the composition of the eukaryotic cellular membrane and its properties. Of note, an alteration of phosphatidylcholine (PC) and phosphatidylethanolamine (PE) ratio has been directly implicated in AD [8], along with a reduction in membrane fluidity of central and peripheral cells [9], thus strengthening the disease’s link with oxidative stress.…”

Section: Introductionmentioning

confidence: 99%

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Impact of ApoE Polymorphism and Physical Activity on Plasma Antioxidant Capability and Erythrocyte Membranes

et al. 2019

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The allele epsilon 4 (ε4) of apolipoprotein E (ApoE) is the strongest genetic risk factor for Alzheimer’s disease (AD). ApoE protein plays a pivotal role in the synthesis and metabolism of amyloid beta (Aβ), the major component of the extracellular plaques that constitute AD pathological hallmarks. Regular exercise is an important preventive/therapeutic tool in aging and AD. Nevertheless, the impact of physical exercise on the well-being of erythrocytes, a good model of oxidative stress and neurodegenerative processes, remains to be investigated, particularly depending on ApoE polymorphism. Herein, we evaluate the oxidative status, Aβ levels, and the membrane’s composition of erythrocytes in a cohort of human subjects. In our hands, the plasma antioxidant capability (AOC), erythrocytes membrane fluidity, and the amount of phosphatidylcholine (PC) were demonstrated to be significantly decreased in the ApoE ε4 genotype and non-active subjects. In contrast, erythrocyte Aβ content and lipid peroxidation increased in ε4 carriers. Regular physical exercise was associated with an increased plasma AOC and membrane fluidity, as well as to a reduced amount of erythrocytes Aβ. Altogether, these data highlight the influence of the ApoE genotype on erythrocytes’ well-being and confirm the positive impact of regular physical exercise.

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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Impact of ApoE Polymorphism and Physical Activity on Plasma Antioxidant Capability and Erythrocyte Membranes

et al. 2019

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“…It has been hypothesized that double aneuploidy results either from two nondisjunctional events in gametogenesis or from a single nondisjunctional event in a trisomic zygote 30,31 . Regarding the autosomal chromosomes, one of the main genes involved in AD, the amyloid precursor protein gene, is located on chromosome 21 32 . Amyloid precursor protein is directly linked to AD pathogenesis, and it was one of the first genes to be associated with chromosomal alterations.…”

Section: Discussionmentioning

confidence: 99%

Investigation of chromosomal alterations in patients with Alzheimer's disease in the state of Amazonas, Brazil

Nunes

Benzaquem

Carvalho

et al. 2019

Arq. Neuro-Psiquiatr.

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Alzheimer's disease (AD) has as its main characteristic the deterioration of cerebral functions. Its etiology is still complex and undefined despite the progress made in understanding its neurological, infectious, biochemical, genetic and cytogenetic mechanisms. Considering this, the aim of this study was to investigate the presence of chromosomal alterations in the peripheral blood lymphocytes, and to verify if there was a high frequency of these alterations in patients diagnosed with AD at the University Hospital GetúLio Vargas Outpatient Clinic Araújo Lima in Manaus, Amazonas, Brazil. Among the nine patients in the AD group, only one patient did not have metaphases with chromosomal alterations (2n = 46,XX), while eight patients with AD showed numerical chromosomal alterations, classified as X chromosome aneupLoidy (2n = 45,X) and double aneupLoidy (2n = 44,X,-X,-10; 2n = 44,X,-X,-13 and 2n = 44,X,-X,-21). In the control group, no chromosomal changes were found in the karyotypes of these individuals. Therefore, the karyotypes of patients with AD undergo chromosomal alterations at different levels. These findings are being described for the first time in the population of Amazonas, and they highlight the importance of the inclusion of cytogenetic investigations in the routine management of patients with AD.

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“…It contains an Aβ-encoding region which is cleaved by a series of secretases: α then γ, or β then γ Proteolytic processing of APP occurs by one of two pathways, the nonamyloidogenic or the amyloidogenic. [12] APP intracellular domain (AICD). AICD and p3 (3kDa) peptide are released into the cytosol and extracellular space, respectively.…”

Section: (B)amyloid Hypothesismentioning

confidence: 99%

Novel Pharmacological Approach to the Treatment of Alzheimer’s Disease

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-²

2022

IJFMR

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Alzheimer's disorder is one of the maximum devastating mind problems of aged humans It is an undertreated and under-identified disorder this is turning into a chief public health problem. The remaining decade has witnessed a progressively growing attempt directed at discovering the etiology of the disease and developing pharmacological treatment An overview of Alzheimer's as a disease state and its pharmacological and non-pharmacological management is provided in the paper. Caring for the person diagnosed with Alzheimer's may be taxing and thus caring for the carer is also described. Currently to be had remedies i.e. Acetylcholinesterase inhibitors (rivastigmine, galantamine, donepezil) and N-methyl d-aspartate receptor antagonist (memantine) contribute minimal impact on the disease and target late aspects of the disease. These tablets slow down the development of the disease, offer symptomatic relief but fail to achieve a definite cure.

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Genetic, Biochemical and Histopathological Aspects of Familiar Alzheimer's Disease

Cited by 8 publications

References 118 publications

Impact of ApoE Polymorphism and Physical Activity on Plasma Antioxidant Capability and Erythrocyte Membranes

Impact of ApoE Polymorphism and Physical Activity on Plasma Antioxidant Capability and Erythrocyte Membranes

Investigation of chromosomal alterations in patients with Alzheimer's disease in the state of Amazonas, Brazil

Novel Pharmacological Approach to the Treatment of Alzheimer’s Disease

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