Lack of C9orf72 Repeat Expansion in Taiwanese Patients with Mixed Neurodegenerative Disorders

Lin, Chin-Hsien; Chen, Ta Fu; Chiu, Ming‐Jang; Lin, Han-I; Wu, Ruey‐Meei

doi:10.3389/fneur.2014.00059

Cited by 15 publications

(21 citation statements)

References 29 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…The inclusion of baseline genomics data in such a cluster analyses could result in the identification of even more homogenous sets of MCI subgroups. One of the most important genetic subgrouping that has been relatively overlooked in the laboratory study of AD is the effect of gender – most rodent studies have been in male mice and only a small number of biomarker studies have tested for sex differences 6, 7 . Our analyses show that rapid MCI decliners in both sexes had worse baseline cognition, higher levels of cortical amyloid and tau pathology as well as smaller volumes of hippocampal and entorhinal cortices.…”

Section: Discussionmentioning

confidence: 99%

“…For example, one study found that the age-specific risk of AD was almost two-fold greater in women than men (17.2% versus 9.1% at age 65 years and 28.5% versus 10.2% at age 75 years) 8 and some other studies find that sex-differences become most prominent among eighty year olds 7 . Potential mechanisms to explain such differences include greater effects of the Apolipoprotein E4 allele in women, sex hormones (such as estrogen), lower cognitive reserve, and differences in occupational or educational attainment (reviewed in refs 6 and 7. Sex differences in immune system responsivity, MRI brain atrophy rates 9 and effects of plaque-tangle pathology 10 have also been reported.…”

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

“…In addition to individual heterogeneity, the study of potential sex differences in AD epidemiology, biology and therapeutics has been a relatively neglected area of research (reviewed in refs 6 and 7. The reported higher prevalence of Alzheimer’s disease (AD) in women had been attributed previously to longer female life expectancy or a detection bias but some, but not all, recent findings suggest that older women may be at greater risk for AD than men 6, 7 . For example, one study found that the age-specific risk of AD was almost two-fold greater in women than men (17.2% versus 9.1% at age 65 years and 28.5% versus 10.2% at age 75 years) 8 and some other studies find that sex-differences become most prominent among eighty year olds 7 .…”

Section: Introductionmentioning

confidence: 99%

“…The reported higher prevalence of Alzheimer’s disease (AD) in women had been attributed previously to longer female life expectancy or a detection bias but some, but not all, recent findings suggest that older women may be at greater risk for AD than men 6, 7 . For example, one study found that the age-specific risk of AD was almost two-fold greater in women than men (17.2% versus 9.1% at age 65 years and 28.5% versus 10.2% at age 75 years) 8 and some other studies find that sex-differences become most prominent among eighty year olds 7 . Potential mechanisms to explain such differences include greater effects of the Apolipoprotein E4 allele in women, sex hormones (such as estrogen), lower cognitive reserve, and differences in occupational or educational attainment (reviewed in refs 6 and 7.…”

Section: Introductionmentioning

confidence: 99%

See 4 more Smart Citations

Identification of clusters of rapid and slow decliners among subjects at risk for Alzheimer’s disease

Gamberger

Lavrač

Srivatsa

et al. 2017

Sci Rep

View full text Add to dashboard Cite

The heterogeneity of Alzheimer’s disease contributes to the high failure rate of prior clinical trials. We analyzed 5-year longitudinal outcomes and biomarker data from 562 subjects with mild cognitive impairment (MCI) from two national studies (ADNI) using a novel multilayer clustering algorithm. The algorithm identified homogenous clusters of MCI subjects with markedly different prognostic cognitive trajectories. A cluster of 240 rapid decliners had 2-fold greater atrophy and progressed to dementia at almost 5 times the rate of a cluster of 184 slow decliners. A classifier for identifying rapid decliners in one study showed high sensitivity and specificity in the second study. Characterizing subgroups of at risk subjects, with diverse prognostic outcomes, may provide novel mechanistic insights and facilitate clinical trials of drugs to delay the onset of AD.

show abstract

Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

See 3 more Smart Citations

Identification of clusters of rapid and slow decliners among subjects at risk for Alzheimer’s disease

Gamberger

Lavrač

Srivatsa

et al. 2017

Sci Rep

View full text Add to dashboard Cite

show abstract

Genetic study ofyoung‐onsetdementia using targeted gene panel sequencing in Taiwan

Hsu

Lin

Chen

et al. 2021

American J of Med Genetics Pt B

View full text Add to dashboard Cite

Recent genetic progress allows the molecular diagnosis of young‐onset dementia, including Alzheimer's disease (AD) and frontotemporal dementia (FTD). We aimed to identify the mutational and clinical spectra of causal genes in a Taiwanese cohort of young‐onset dementia. Ninety‐one patients with young‐onset dementia and 22 age/gender‐matched controls were recruited. Genetic causes were identified by a targeted panel containing 90 causative genes for AD, FTD, and related neurodegenerative disorders. Plasma biomarkers, including total tau, Aβ42, and Aβ40, were assayed. Molecular amyloid and tau PET scans were performed in some patients carrying mutations. Nine of 52 patients (17.3%) with young‐onset AD had mutations: 2 (22.2%), 4 (44.5%), 2 (22.2%), and 1 (11.1%) in APP, PSEN1, PSEN2, and TREM2, respectively. Two of 33 patients (6.1%) with young‐onset FTD had mutations in MAPT and LRRK2. Three of the 6 patients (50.0%) with possible FTD combined with other neurodegenerative disorders had individual mutations in APP, PSEN2, or MAPT. Patients with PSEN1 mutations had earlier onset of disease than those without mutations (p = .02). Plasma level of total tau was increased and Aβ42 and Aβ40 levels decreased in all groups of dementia patients compared to controls. Our findings provide a genetic spectrum of young‐onset dementia in our population.

show abstract

C9orf72 and its Relevance in Parkinsonism and Movement Disorders: A Comprehensive Review of the Literature

Bourinaris

Houlden

2018

Movement Disord Clin Pract

View full text Add to dashboard Cite

Background The C9orf72 hexanucleotide expansion is one of the latest discovered repeat expansion disorders related to neurodegeneration. Its association with the FTD/ALS spectrum disorders is well established, and it is considered to be one of the leading related genes. It has also been reported as a possible cause of several other phenotypes, including parkinsonism and other movement disorders. Its significance, though outside the FTD/ALS spectrum, is not well defined. Methods A comprehensive search of the literature was performed. All relevant papers, including reviews and case series/reports on movement disorder phenotypes reported with the C9orf72 repeat expansion, were reviewed. Data on frequency, natural history, phenotype, genetics, and possible underlying mechanisms were assessed. Results and Discussion In a number of studies, C9orf72 accounts for a small fraction of typical PD. Atypical parkinsonian syndromes, including CBS, PSP, and MSA have also been reported. Features that increase the probability of positive testing include early cognitive and/or behavioral symptoms, positive family history of ALS or FTD, and the presence of UMN and LMN signs. Furthermore, several studies conclude that C9orf72 is the most common cause of HD‐phenocopies. Interestingly, many cases with the parkinsonian phenotype that bear an intermediate range of repeats are also reported, questioning the direct causal role of C9orf72 and suggesting the possibility of being a susceptibility factor, while the presence of the expansion in normal controls questions its clinical significance. Finally, studies on pathology reveal a distinctive broad range of C9orf72‐related neurodegeneration that could explain the wide phenotypic variation.

show abstract

Lack of C9orf72 Repeat Expansion in Taiwanese Patients with Mixed Neurodegenerative Disorders

Cited by 15 publications

References 29 publications

Identification of clusters of rapid and slow decliners among subjects at risk for Alzheimer’s disease

Identification of clusters of rapid and slow decliners among subjects at risk for Alzheimer’s disease

Genetic study ofyoung‐onsetdementia using targeted gene panel sequencing in Taiwan

C9orf72 and its Relevance in Parkinsonism and Movement Disorders: A Comprehensive Review of the Literature

Contact Info

Product

Resources

About