Genetics of Alzheimer's Disease: An Insight Into Presenilins and Apolipoprotein E Instigated Neurodegeneration

Obulesu, Magisetty; Somashekhar, R.; Venu, R.

doi:10.3109/00207454.2010.551432

Cited by 20 publications

(7 citation statements)

References 80 publications

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“…Importantly, we explored eleven mutations to be classified as variants of uncertain significance, which may contribute to the disease occurrence. Unlike PSEN1 carriers, mutations in PSEN2 cause AD with variable penetrance and have a later onset age [ 36 ]. Two Chinese patients and one Korean patient with PSEN2 p.V214L have been identified in the Chinese AD cohort consisting of 61 patients and Korean EOAD cohort consisting of 104 patients respectively, indicating that PSEN2 p.V214L could have associations with the risks of developing AD in the Asian population.…”

Section: Discussionmentioning

confidence: 99%

The Whole Exome Sequencing Clarifies the Genotype- Phenotype Correlations in Patients with Early-Onset Dementia

Xu¹,

Liu²,

Shen³

et al. 2018

Aging and disease

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Our study aimed to identify the underlying causes in patients with early onset dementia by clinical and genetic exploration. We recruited a group of 38 patients with early-onset dementia. Firstly, hexanucleotide repeat expansions in C9ORF72 gene were screened in all subjects to exclude the possibility of copy number variation. Then, the whole exome sequencing (WES) was conducted, and the data were analyzed focusing on 89 dementia-related causing and susceptible genes. The effects of identified variants were classified according to the American College of Medical Genetics and Genomics (ACMG) standards and guidelines. There were no pathogenic expansions in C9ORF72 detected. According to the ACMG standards and guidelines, we identified five known pathogenic mutations, PSEN1 P284L, PSEN1c.857-1G>A, PSEN1 I143T, PSEN1 G209E and MAPT G389R, and one novel pathogenic mutation APP K687N. All these mutations caused dementia with the mean onset age of 38.3 (range from 27 to 51) and rapid progression. Eleven variants with uncertain significance were also detected and needed further verification. The clinical phenotypes of dementia are heterogeneous, with both onset ages and clinical features being influenced by mutation position as well as the causative gene. WES can serve as efficient diagnostic tools for different heterogeneous dementia.

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Section: Discussionmentioning

confidence: 99%

The Whole Exome Sequencing Clarifies the Genotype- Phenotype Correlations in Patients with Early-Onset Dementia

Xu¹,

Liu²,

Shen³

et al. 2018

Aging and disease

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“…Mutations in PS1 (and also PS2) were described in the familial form of AD. More than 1000 point mutations in the presenilins are responsible for most of the familial forms of AD [47].…”

Section: Amyloid Cascade Hypothesismentioning

confidence: 99%

Molecular mechanisms of neuropathological changes in Alzheimer’s disease: a review

Šerý¹,

Povová²,

Mı́šek³

et al. 2013

151

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“…Its etiology entails oxidative stress, deposition of extracellular amyloid beta (Ab) plaques, formation of intracellular neurofibrillary tangles (NFTs), metal mediated neurotoxicity, mutations in genes, neuroinflammation, hyperphosphorylation of tau and apoptosis [3][4][5][6][7][8][9]. Apoptosis is the biological process in which a cell keenly proceeds towards death upon receiving definite stimuli [10].…”

Section: Introductionmentioning

confidence: 99%

Apoptosis in Alzheimer’s Disease: An Understanding of the Physiology, Pathology and Therapeutic Avenues

2014

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Alzheimer's disease (AD) is a devastative neurodegenerative disorder with complex etiology. Apoptosis, a biological process that plays an essential role in normal physiology to oust a few cells and contribute to the normal growth, when impaired or influenced by various factors such as Bcl2, Bax, caspases, amyloid beta, tumor necrosis factor-α, amyloid precursor protein intracellular C-terminal domain, reactive oxygen species, perturbation of enzymes leads to deleterious neurodegenerative disorders like AD. There are diverse pathways that provoke manifold events in mitochondria and endoplasmic reticulum (ER) to execute the process of cell death. This review summarizes the crucial apoptotic mechanisms occurring in both mitochondria and ER. It gives substantial summary of the diverse mechanisms studied in vivo and in vitro. A brief account on neuroprotection of several bioactive components, flavonoids and antioxidants of plants against apoptotic events of both mitochondria and ER in both in vitro and in vivo has been discussed. In light of this, the burgeoning need to develop animal models to study the efficacy of various therapeutic effects has been accentuated.

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Genetics of Alzheimer's Disease: An Insight Into Presenilins and Apolipoprotein E Instigated Neurodegeneration

Cited by 20 publications

References 80 publications

The Whole Exome Sequencing Clarifies the Genotype- Phenotype Correlations in Patients with Early-Onset Dementia

The Whole Exome Sequencing Clarifies the Genotype- Phenotype Correlations in Patients with Early-Onset Dementia

Molecular mechanisms of neuropathological changes in Alzheimer’s disease: a review

Apoptosis in Alzheimer’s Disease: An Understanding of the Physiology, Pathology and Therapeutic Avenues

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