Germline DNA copy number variation in individuals with Argyrophilic grain disease reveals CTNS as a plausible candidate gene

Villela, Darine; Kimura, Lilian; Schlesinger, David; Gonçalves, Amanda; Pearson, P. L.; Suemoto, Cláudia Kimie; Pasqualucci, Carlos Augusto; Krepischi, Ana Cristina Victorino; Grinberg, Lea T.; Rosenberg, Carla

doi:10.1590/s1415-47572013000400006

Cited by 7 publications

(4 citation statements)

References 12 publications

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“…To date, no specific genetic locus has been associated with AGD. However, a 40 kb deletion at 17p13.2 encompassing the cystinosin, lysosomal cystine transporter ( CTNS ) gene has recently been described suggesting that this may be a candidate gene for AGD [211]. No mutation has been reported in MAPT in PART, but haplotype analysis demonstrates a strong association with the MAPT H1 haplotype.…”

Section: Tauopathies (Ftld-tau)mentioning

confidence: 99%

Frontotemporal lobar degeneration: defining phenotypic diversity through personalized medicine

et al. 2014

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Frontotemporal lobar degeneration (FTLD) comprises two main classes of neurodegenerative diseases characterized by neuronal/glial proteinaceous inclusions (ie. proteinopathies) including tauopathies (i.e. FTLD-Tau) and TDP-43 proteinopathies (i.e. FTLD-TDP) while other very rare forms of FTLD are known such as FTLD with FUS pathology (FTLD-FUS). This review focuses mainly on FTLD-Tau and FLTD-TDP, which may present as several clinical syndromes: a behavioral/dysexecutive syndrome (behavioral-variant frontotemporal dementia); language disorders (primary progressive aphasia variants); and motor disorders (amyotrophic lateral sclerosis, corticobasal syndrome, progressive supranuclear palsy syndrome). There is considerable heterogeneity in clinical presentations of underlying neuropathology and current clinical criteria do not reliably predict underlying proteinopathies ante-mortem. In contrast, molecular etiologies of hereditary FTLD are consistently associated with specific proteinopathies. These include MAPT mutations with FTLD-Tau and GRN, C9orf72, VCP and TARDBP with FTLD-TDP. The last decade has seen a rapid expansion in our knowledge of the molecular pathologies associated with this clinically and neuropathologically heterogeneous group of FTLD diseases. Moreover, in view of current limitations to reliably diagnose specific FTLD neuropathologies prior to autopsy, we summarize the current state of the science in FTLD biomarker research including neuroimaging, biofluid and genetic analyses. We propose that combining several of these biomarker modalities will improve diagnostic specificity in FTLD through a personalized medicine approach. The goals of these efforts are to enhance power for clinical trials focused on slowing or preventing progression of spread of tau, TDP-43 and other FTLD-associated pathologies and work towards the goal of defining clinical endophenotypes of FTD.

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Section: Tauopathies (Ftld-tau)mentioning

confidence: 99%

Frontotemporal lobar degeneration: defining phenotypic diversity through personalized medicine

et al. 2014

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“…Although AGD remains a predominantly sporadic disease, recent studies described 2 rare microtubule-associated protein tau gene mutations (MAPT S305I and S305S) causing pathological features consistent with AGD in individuals with memory decline and behavioral changes (26,27). Furthermore, AGD is associated with DNA copy number variations at 17p13.2 (28).…”

Section: Introductionmentioning

confidence: 99%

Argyrophilic Grain Disease: Demographics, Clinical, and Neuropathological Features From a Large Autopsy Study

Rodriguez

Suemoto

Molina

et al. 2016

J Neuropathol Exp Neurol

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Argyrophilic grain disease (AGD) is a frequent late-onset, 4-repeat tauopathy reported in Caucasians with high educational attainment. Little is known about AGD in non-Caucasians or in those with low educational attainment. We describe AGD demographics, clinical, and neuropathological features in a multiethnic cohort of 983 subjects ≥50 years of age from São Paulo, Brazil. Clinical data were collected through semistructured interviews with an informant and included in the Informant Questionnaire on Cognitive Decline in the Elderly, the Clinical Dementia Rating, and the Neuropsychiatric Inventory. Neuropathologic assessment relied on internationally accepted criteria. AGD was frequent (15.2%) and was the only neuropathological diagnosis in 8.9% of all cases (mean, 78.9 ± 9.4 years); it rarely occurred as an isolated neuropathological finding. AGD was associated with older age, lower socioeconomic status (SES), and appetite disorders. This is the first study of demographic, clinical, and neuropathological aspects of AGD in different ethnicities and subjects from all socioeconomic strata. The results suggest that prospective studies of AGD patients include levels of hormones related to appetite control as possible antemortem markers. Moreover, understanding the mechanisms behind higher susceptibility to AGD of low SES subjects may disclose novel environmental risk factors for AGD and other neurodegenerative diseases.

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“… 2 as a strong candidate for causing AGD. 74 Studies have demonstrated the role of CNV in the etiology of several neuropsychiatric disorders. 75 Unlike other 4R tauopathies such as PSP and CBD, there are controversies over the relationship of the tau H1 haplotype with positive and negative results.…”

Section: Introductionmentioning

confidence: 99%

Argyrophilic grain disease: An underestimated tauopathy

Rodriguez

Grinberg

2015

Dement. neuropsychol.

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Argyrophilic grain disease (AGD) is an under-recognized, distinct, highly frequent sporadic tauopathy, with a prevalence reaching 31.3% in centenarians. The most common AGD manifestation is slowly progressive amnestic mild cognitive impairment, accompanied by a high prevalence of neuropsychiatric symptoms. AGD diagnosis can only be achieved postmortem based on the finding of its three main pathologic features: argyrophilic grains, oligodendrocytic coiled bodies and neuronal pretangles. AGD is frequently seen together with Alzheimer's disease-type pathology or in association with other neurodegenerative diseases. Recent studies suggest that AGD may be a defense mechanism against the spread of other neuropathological entities, particularly Alzheimer's disease. This review aims to provide an in-depth overview of the current understanding on AGD.

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Germline DNA copy number variation in individuals with Argyrophilic grain disease reveals CTNS as a plausible candidate gene

Cited by 7 publications

References 12 publications

Frontotemporal lobar degeneration: defining phenotypic diversity through personalized medicine

Frontotemporal lobar degeneration: defining phenotypic diversity through personalized medicine

Argyrophilic Grain Disease: Demographics, Clinical, and Neuropathological Features From a Large Autopsy Study

Argyrophilic grain disease: An underestimated tauopathy

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