Co-occurrence of Sporadic Parkinsonism and Late-Onset Alzheimer's Disease in a Brazilian Male with the<i>LRRK2</i>p.G2019S Mutation

Santos-Rebouças, Cíntia Barros; Abdalla, Cláudia Bueno; Baldi, Fabio; Martins, Paloma Águia; Corrêa, Juliana C.; Gonçalves, Andressa Pereira; Cunha, Marcela Sabino; Borges, Margarete Borges de; Pereira, Joäo Santos; Laks, Jérson; Pimentel, Márcia Mattos Gonçalves

doi:10.1089/gte.2008.0042

Cited by 16 publications

(6 citation statements)

References 27 publications

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“…DISCUSSION Our findings are in agreement with the majority of reports of the clinical features of LRRK2-associated PD, which indicate that the phenotype is not distinguishable from iPD. There have been individual exceptions to this, however; atypical cases with supranuclear gaze palsies, 8 prominent dementia, 9 or psychosis unrelated to medications. 10 Tremor was a more common presenting feature in our LRRK2 group compared with iPD, and this was also found in a large international study.…”

Section: Figurementioning

confidence: 99%

Phenotype in parkinsonian and nonparkinsonian LRRK2 G2019S mutation carriers

Marras¹,

Schuele²,

Munhoz³

et al. 2011

Neurology

159

121

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Section: Figurementioning

confidence: 99%

Phenotype in parkinsonian and nonparkinsonian LRRK2 G2019S mutation carriers

Marras¹,

Schuele²,

Munhoz³

et al. 2011

Neurology

159

121

View full text Add to dashboard Cite

show abstract

“…The incidence of tremor, however, seems to be elevated in LRRK2 carriers indicating that LRRK2 mutations most likely lead to tremor-dominant disease [Haugarvoll et al, 2008;Nuytemans et al, 2008;Paisan-Ruiz et al, 2004]. On the other hand, isolated studies have also reported LRRK2 mutations in carriers with a clinical diagnosis of sporadic PD with late-onset AD as well as CBD, PSP, or frontotemporal dementia (FTD) [Chen-Plotkin et al, 2008;Santos-Reboucas et al, 2008;Spanaki et al, 2006].…”

Section: Discussionmentioning

confidence: 99%

Genetic etiology of Parkinson disease associated with mutations in the SNCA, PARK2, PINK1, PARK7, and LRRK2 genes: a mutation update

et al. 2010

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To date, molecular genetic analyses have identified over 500 distinct DNA variants in five disease genes associated with familial Parkinson disease; α-synuclein (SNCA), parkin (PARK2), PTEN-induced putative kinase 1 (PINK1), DJ-1 (PARK7), and Leucine-rich repeat kinase 2 (LRRK2). These genetic variants include ∼82% simple mutations and ∼18% copy number variations. Some mutation subtypes are likely underestimated because only few studies reported extensive mutation analyses of all five genes, by both exonic sequencing and dosage analyses. Here we present an update of all mutations published to date in the literature, systematically organized in a novel mutation database (http://www.molgen.ua.ac.be/PDmutDB). In addition, we address the biological relevance of putative pathogenic mutations. This review emphasizes the need for comprehensive genetic screening of Parkinson patients followed by an insightful study of the functional relevance of observed genetic variants. Moreover, while capturing existing data from the literature it became apparent that several of the five Parkinson genes were also contributing to the genetic etiology of other Lewy Body Diseases and Parkinson-plus syndromes, indicating that mutation screening is recommendable in these patient groups. Hum Mutat 31:763–780, 2010. © 2010 Wiley-Liss, Inc.

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“…However, to date, most genetic screens have been limited to PD clinic populations, with only a few studies referring to other neurodegenerative diseases. LRRK2 mutation has been assumed to play an upstream influence on the etiology of not just PD but also several α-synuclein and tau pathologies, including Alzheimer disease (AD) [ 37 ]. A research reported two LRRK2 mutation carriers who showed cognitive impairment, leading to clinical diagnoses of corticobasal syndrome (CBS) and primary progressive aphasia (PPA), a subtype of frontotemporal dementia (FTD).…”

Section: Clinical Features Of Lrrk2-associated Parkinsonismmentioning

confidence: 99%

The role of the LRRK2 gene in Parkinsonism

Tan

2014

Mol Neurodegeneration

210

132

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Parkinson’s disease (PD), like many common age-related conditions, has been recognized to have a substantial genetic component. Multiple lines of evidence suggest that Leucine-rich repeat kinase 2 (LRRK2) is a crucial factor to understanding the etiology of PD. LRRK2 is a large, widely expressed, multi-domain and multifunctional protein. LRRK2 mutations are the major cause to inherited and sporadic PD. In this review, we discuss the pathology and clinical features which show diversity and variability of LRRK2-associated PD. In addition, we do a thorough literature review and provide theoretical data for gene counseling. Further, we present the evidence linking LRRK2 to various possible pathogenic mechanism of PD such as α-synuclein, tau, inflammatory response, oxidative stress, mitochondrial dysfunction, synaptic dysfunction as well as autophagy-lysosomal system. Based on the above work, we investigate activities both within GTPase and outside enzymatic regions in order to obtain a potential therapeutic approach to solve the LRRK2 problem.

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Co-occurrence of Sporadic Parkinsonism and Late-Onset Alzheimer's Disease in a Brazilian Male with theLRRK2p.G2019S Mutation

Cited by 16 publications

References 27 publications

Phenotype in parkinsonian and nonparkinsonian LRRK2 G2019S mutation carriers

Phenotype in parkinsonian and nonparkinsonian LRRK2 G2019S mutation carriers

Genetic etiology of Parkinson disease associated with mutations in the SNCA, PARK2, PINK1, PARK7, and LRRK2 genes: a mutation update

The role of the LRRK2 gene in Parkinsonism

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