A novel V272D presenilin mutation associated with logopenia, disorientation, and apraxia in an autosomal-dominant Alzheimer's disease family

Mengel, David; Liu, Lei; Yamamoto, Raina; Zülow, Stefan; Deuschl, Cornelius; Hermann, Dirk M.; Zerr, Inga; Selkoe, Dennis J.; Dodel, Richard

doi:10.1016/j.neurobiolaging.2019.07.002

Cited by 4 publications

(2 citation statements)

References 12 publications

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“…In fact, it has been proven by experiments that oxidative stress is a predictable phenomenon in the pathogenesis of AD. Amyloid β proteins, which are caused by abnormalities in the PSEN1 gene, which play an active role in AD, are also thought to play a critical role in oxidative stress [ 30 ] . Shoeb et al showed increased expression of the PSEN1 gene by oxidative stress [ 31 ] .…”

Section: Discussionmentioning

confidence: 99%

Oxidative Stress and Changes of Important Metabolic Gene Expressions as a Potential Biomarker in the Diagnosis of Atherosclerosis in Leukocytes

Işık¹,

Tunç²,

Beydemır³

2022

Braz J Cardiovasc Surg

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Introduction Presenilin 1 (PSEN1), catalase (CAT), glutathione-S-transferase (GST) and paraoxonase 1 (PON1) play a vital role in prediction, diagnosis and therapy of metabolic disorders. Methods Metabolic enzyme activities and lipid peroxidation in serum of cerebrovascular diseases (CVD) and coronary artery diseases were measured by spectrophotometric methods. mRNA was isolated from leukocytes of the patient group and healthy adult patients. Quantitative gene expression of PSEN1, CAT and GST mRNA was identified by quantitative real-time polymerase chain reaction (qPCR). Results The PSEN1, CAT and GST expression in patients showed significant differences compared to the control group. PSEN1 expression in leukocytes was significantly about twice as high as that of the control group in patients with CVD. The GST, CAT and PON1 activity showed significant differences in patient groups compared to the control group. Conclusion The mRNA expression levels can be used as a potential biomarker in the diagnosis of atherosclerosis that occurs as a result of the metabolic disorder. In atherosclerotic patients, antioxidant status is independently related to an increased risk of cardiovascular events. Antioxidant activities and mRNA expressions may have predictive value, as well as available risk factors.

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Section: Discussionmentioning

confidence: 99%

Oxidative Stress and Changes of Important Metabolic Gene Expressions as a Potential Biomarker in the Diagnosis of Atherosclerosis in Leukocytes

Işık¹,

Tunç²,

Beydemır³

2022

Braz J Cardiovasc Surg

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“…In the final stages, gait disturbances, seizures, and myoclonus were frequent [ 24 ]. Later on, the AD phenotype of PSEN1 has proved to be very broad, including not only cognitive decline, behavioral and psychiatric symptoms of dementia but also parkinsonism, myoclonus and epileptic seizures, spastic paraparesis, features suggestive of the phenotype of frontotemporal dementia, progressive aphasia, and cerebellar ataxia [ 23 , 25 ]. It was reported that atypical symptoms occurred more often in mutations after codon 200 of PSEN1 [ 4 , 6 ].…”

Section: Discussionmentioning

confidence: 99%

Clinical Phenotype and Mutation Spectrum of Alzheimer’s Disease with Causative Genetic Mutation in a Chinese Cohort

Mao

Dong

et al. 2021

CAR

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Background: Alzheimer’s disease with a causative genetic mutation (AD-CGM) is an un- common form, characterized by a heterogeneous clinical phenotype and variations in the genotype of racial groups affected. Objective: We aimed to systemically describe the phenotype variance and mutation spectrum in the large sample size of the Peking Union Medical College Hospital (PUMCH) cohort, Beijing, China. Method: Next-generation sequencing (NGS) was carried out in 1108 patients diagnosed with dementia. A total of 40 Han Chinese patients with three AD gene mutations were enrolled. A systemic review of all the patients was performed, including clinical history, neurocognitive assessment, brain magnetic resonance imaging, and cerebrospinal fluid (CSF) biomarkers. Results: We studied the following gene mutation variants: 12 AβPP, 13 PSEN1, and 9 PSEN2, and 23 among them were novel. Most of them were early-onset, but PSEN1 mutation carriers had the youngest onset age. The commonest symptoms were similar to those of AD, including an amnestic syndrome, followed by psychiatric symptoms and movement disorder. On MRI, parietal and posterior temporal atrophy was prominent in PSEN1 and PSEN2 mutation carriers, while AβPP mutation carriers had more vascular changes. The CSF biomarkers profile was indistinguishable from sporadic AD. Conclusion: We identified a small group of AD-CGM subjects representing 3.6% among more than 1000 demented patients in the PUMCH cohort. These subjects usually presented with early-onset de- mentia and exhibited significant clinical and genetic heterogeneity. Identification required complete screening of genetic mutations using NGS. Although family history was usually present, we found non-familial cases of all three genetic mutations.

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Genetic Variants Associated With Alzheimer Disease in the 22 Arab Countries

Al-Thani

Ahmad

Younes

et al. 2021

Alzheimer Disease &Amp; Associated Disorders

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Background and Aims: Alzheimer disease (AD) is a progressive and complex neurodegenerative disease. Approximately 70% of AD risk is attributed to genetic risk factors, including variants in amyloid precursor protein (APP), presenilin 1 (PSEN1), and presenilin 2 (PSEN2) genes. Several studies have revealed a considerable number of candidate loci and genes for AD among different ethnic populations. However, the outcomes of these studies have been inconsistent. In this study, we aimed to investigate the spectrum of variants that are associated with the onset and development of AD among 22 Arab countries. Methodology: We systematically searched 4 literature databases (Science Direct, Scopus, PubMed, and Web of Science) from the date of inception until July 2020 using various search terms to obtain all the reported genetic data on Arab AD cases. Results: In total, 18 studies were included, comprising a total of 2173 individuals, of whom 888 were clinically diagnosed AD patients and were genetically tested for genes and variants associated with AD. A total of 27 variants in 8 genes were found to be associated with AD. Of these variants, 17 were unique to the Arab population and 10 were shared with other ethnic groups. Conclusions: There is a dearth of studies on the genetics of AD in the Arab world. There seems to be distinctive genetic and clinical susceptibility profiles for Arab patients with AD.

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A novel V272D presenilin mutation associated with logopenia, disorientation, and apraxia in an autosomal-dominant Alzheimer's disease family

Cited by 4 publications

References 12 publications

Oxidative Stress and Changes of Important Metabolic Gene Expressions as a Potential Biomarker in the Diagnosis of Atherosclerosis in Leukocytes

Oxidative Stress and Changes of Important Metabolic Gene Expressions as a Potential Biomarker in the Diagnosis of Atherosclerosis in Leukocytes

Clinical Phenotype and Mutation Spectrum of Alzheimer’s Disease with Causative Genetic Mutation in a Chinese Cohort

Genetic Variants Associated With Alzheimer Disease in the 22 Arab Countries

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