Pathogenic PSEN1 Glu184Gly Mutation in a Family from Thailand with Probable Autosomal Dominant Early Onset Alzheimer’s Disease

Senanarong, Vorapun; An, Seong Soo A.; Van, Giau Vo; Limwongse, Chanin; Bagyinszky, Eva; Kim, SangYun

doi:10.3390/diagnostics10030135

Cited by 3 publications

(2 citation statements)

References 40 publications

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“…For the PSEN1 M233T and PSEN2 M239I mutations we used the mean age at onset reported by Ryman20 (33.7 and 50.7 y, respectively), and for the MAPT P301L, GRN T272fs and GRN C157fs, those reported by Morris21 (53.0, 62.7, and 58.4 y, respectively). For the PSEN1 G184G genetic mutation, the mean age of onset (47.7 y) was computed from literature 22–24. For the PSEN1 L392V genetic mutation, we did not find pertinent information in the literature and estimated age at onset (44.0 y) from data kindly provided by the Dominantly Inherited Alzheimer Network (DIAN) Expanded Registry of the Washington University in Saint Louis (personal communication).…”

Section: Methodsmentioning

confidence: 99%

“…For the PSEN1 G184G genetic mutation, the mean age of onset (47.7 y) was computed from literature. [22][23][24] For the PSEN1 L392V genetic mutation, we did not find pertinent information in the literature and estimated age at onset (44.0 y) from data kindly provided by the Dominantly Inherited Alzheimer Network (DIAN) Expanded Registry of the Washington University in Saint Louis (personal communication).…”

Section: Methodsmentioning

confidence: 99%

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Psychological Impact of Predictive Genetic Testing for Inherited Alzheimer Disease and Frontotemporal Dementia

Galluzzi¹,

Mega²,

Fede³

et al. 2022

Alzheimer Disease &Amp; Associated Disorders

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Aim: Our aim was to evaluate the psychological impact of predictive genetic testing in individuals at-risk for inherited dementia who underwent a structured counseling and testing protocol. Methods:Participants were healthy at-risk relatives from families with at least one affected patient, in whom a disease-associated genetic variant had been ascertained. A comprehensive psychological assessment (personality, anxiety and depression, quality of life, coping strategies, resilience and health-related beliefs) was administered at baseline, at 6 months and 12 months follow-up.Results: Twenty-four participants from 13 families were included. Sixteen participants underwent blood sampling and genetic analysis; 6 resulted to be carriers of pathogenic variants (1 in PSEN1, 1 in PSEN2, 4 in GRN). Carriers showed higher score on the Resilience Scale for Adults (RSA)social competence, and on Multidimensional Health Locus of Controlinternal, than noncarriers (P = 0.03 for both). Ten atrisk relatives who completed the follow-up showed improvement in RSAplanned future (P = 0.01) with respect to baseline. Discussion: Our case series showed that at-risk individuals undergoing predictive testing showed benefit on personal life and no detrimental impact on a broad range of psychological outcomes. Higher social skills and lower internal health locus of control in carriers may be an early psychological correlate of preclinical dementia.

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Section: Methodsmentioning

confidence: 99%

Section: Methodsmentioning

confidence: 99%

Psychological Impact of Predictive Genetic Testing for Inherited Alzheimer Disease and Frontotemporal Dementia

Galluzzi¹,

Mega²,

Fede³

et al. 2022

Alzheimer Disease &Amp; Associated Disorders

View full text Add to dashboard Cite

show abstract

The Relationship of Anxiety with Alzheimer’s Disease: A Narrative Review

Patel

Masurkar

2021

CAR

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Background: There is an increased effort to better understand neuropsychiatric symptoms of Alzheimer’s disease (AD) as an important feature of symptomatic burden as well as potential modi- fiable factors of the disease process. Anxiety is one of the most common neuropsychiatric symptoms in Alzheimer’s disease (AD). A growing body of work has emerged that addresses the epidemiology and biological correlations of anxiety in AD. Objective and Methods: Here, we review human studies in research and clinical cohorts that examined anxiety in AD. We focused on work related to prevalence across AD stages, correlation with established biomarkers, relationship with AD neuropathology and genetic risk factors, and impact on progression. Results: Anxiety is prominent in the early stages and increases across the spectrum of functional stages. Biomarker relationships are strongest at the level of FDG-PET and amyloid measured via PET or cerebrospinal fluid analysis. Neuropathologically, anxiety emerges with early Braak stage tau pathology. The presence of the apolipoprotein E e4 allele is associated with increased anxiety at all stages, most notably at mild cognitive impairment. Anxiety portended a faster progression at all pre-dementia stages. Conclusion: This body of work suggests a close biological relationship between anxiety and AD that begins in early stages and influences functional decline. As such, we discuss future work that would improve our understanding of this relationship and test the validity of anxiolytic treatment as disease modifying therapy for AD.

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Genetics, Functions, and Clinical Impact of Presenilin-1 (PSEN1) Gene

Bagaria

Bagyinszky

2022

IJMS

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Presenilin-1 (PSEN1) has been verified as an important causative factor for early onset Alzheimer’s disease (EOAD). PSEN1 is a part of γ-secretase, and in addition to amyloid precursor protein (APP) cleavage, it can also affect other processes, such as Notch signaling, β-cadherin processing, and calcium metabolism. Several motifs and residues have been identified in PSEN1, which may play a significant role in γ-secretase mechanisms, such as the WNF, GxGD, and PALP motifs. More than 300 mutations have been described in PSEN1; however, the clinical phenotypes related to these mutations may be diverse. In addition to classical EOAD, patients with PSEN1 mutations regularly present with atypical phenotypic symptoms, such as spasticity, seizures, and visual impairment. In vivo and in vitro studies were performed to verify the effect of PSEN1 mutations on EOAD. The pathogenic nature of PSEN1 mutations can be categorized according to the ACMG-AMP guidelines; however, some mutations could not be categorized because they were detected only in a single case, and their presence could not be confirmed in family members. Genetic modifiers, therefore, may play a critical role in the age of disease onset and clinical phenotypes of PSEN1 mutations. This review introduces the role of PSEN1 in γ-secretase, the clinical phenotypes related to its mutations, and possible significant residues of the protein.

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Pathogenic PSEN1 Glu184Gly Mutation in a Family from Thailand with Probable Autosomal Dominant Early Onset Alzheimer’s Disease

Cited by 3 publications

References 40 publications

Psychological Impact of Predictive Genetic Testing for Inherited Alzheimer Disease and Frontotemporal Dementia

Psychological Impact of Predictive Genetic Testing for Inherited Alzheimer Disease and Frontotemporal Dementia

The Relationship of Anxiety with Alzheimer’s Disease: A Narrative Review

Genetics, Functions, and Clinical Impact of Presenilin-1 (PSEN1) Gene

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