LRRK2p.G2019S Mutation Is Not Common among Alzheimer’s Disease Patients in Brazil

Abstract

Mutations in the leucine-rich repeat kinase 2 (LRRK2) gene have emerged as a potential common cause for both sporadic and familial Parkinson’s Disease (PD) in different populations. The pleomorphic features exhibited by LRRK2 mutation carriers and the central role of Lrrk2 protein in the proper functioning of central nervous system suggest that mutations in this protein might be involved in multiple cellular processes leading to other neurodegenerative disorders than PD. The location of LRRK2 gene on chromosome 12, close to a linkage peak for familial late-onset Alzheimer’s Disease (AD), highlights that LRRK2 mutations might be involved in AD pathogenesis. We screened the most common LRRK2 mutation (p.G2019S) in a series of 180 consecutive patients clinically diagnosed with Alzheimer Disease (AD). We identified the p.G2019S in one AD patient with no PD signs, indicating that this mutation is not a common etiological factor for AD in our population (0.5%), corroborating recent data found in Norwegian, North American, Chinese and Italian populations. Nevertheless, these observations together with new information about the Lrrk2 critical multifunctionality do not rule out the possible influence of other variants within LRRK2 in AD, so that other screenings focusing in the whole extension of the LRRK2 using larger sized confirmed AD sample are urgently needed.

LRRK2 at the Crossroad Between Autophagy and Microtubule Trafficking

“…Regarding neurodegenerative disorders, a study from 2005 screened for G2019S lrrk2 mutation in a series of patients with PD, Alzheimer’s disease (AD), progressive supranuclear palsy, multiple system atrophy, and frontotemporal dementia, as well as in neurologically normal controls, and the mutation was found only in PD patients and not in those with other neurodegenerative diseases (Hernandez and others 2005). In several studies the most common LRRK2 mutation, G2019S, was shown not to be a common cause of AD (Santos-Reboucas and others 2009; Zabetian and others 2006).…”

A meta-analysis of leucine-rich repeat kinase 2 (LRRK2) polymorphisms in Alzheimer’s disease

“…The information of the articles involved in the meta-analysis is shown in Table I. Four studies [8,10,17,21] reported the patients/controls from Singapore, two studies [1,9] from China, and also Taiwan [2], England [11], Brazil [15], Norway [19], Italy [18], Europe/South America [5], and the USA [20], one study each. Four studies [1,2,9,17] checked the distributions of rs34778348 polymorphism, three studies [1,9,21] rs33949390 polymorphism, and two studies [1,9] rs7308720 polymorphism in the patients with AD and the controls.…”

“…Four studies [1,2,9,17] checked the distributions of rs34778348 polymorphism, three studies [1,9,21] rs33949390 polymorphism, and two studies [1,9] rs7308720 polymorphism in the patients with AD and the controls. Out of seven studies [1,5,8,15,[18][19][20] reporting the distributions of rs34637584 polymorphism, just two studies [1,5] reported this polymorphism in the patients with AD and the controls. Out of two studies [1,8] reporting rs35870237 polymorphism, just one study [1] reported this polymorphism in both groups.…”

“…Two studies [10,11] reported that the p.N551K (rs7308720) mutation occurred in 16.9% of patients with AD and 16.1% of controls. Seven studies [1,5,8,15,[18][19][20] included 2772 patients and 3499 controls and found that p.G2019S (rs34637584) mutation occurred in 0.36% of patients and none of controls. In addition, p.I2020T (rs35870237) mutation was reported in none of the patients and controls.…”

The LRRK2 R1628P Variant Plays a Protective Role in Han Chinese Population with Alzheimer's Disease

“…Despite a plausible role of LRRK2 dysfunction in neurodegenerative diseases such as PD and AD, most research to date has failed to find an association between LRRK2 mutations/variants (e.g., G2019S and I2020T, the most common mutations in PD and one Asian‐specific variant G2385R) and AD in different ethnic groups including Chinese, Brazilian, Ashkenazi Jewish, Italian, and Norwegian . To date, the only exception has been a case–control study in 217 patients with AD and 668 controls in Singapore population .…”