Affiliations: Departamento de Genética, Universidade do Estado
do Rio de Janeiro, Rio de Janeiro, Brazil | Núcleo de Atenção ao Idoso, Universidade
do Estado do Rio de Janeiro, Brazil | Instituto de Psiquiatria, Universidade Federal do Rio
de Janeiro, Brazil | Departamento de Biologia Molecular, Faculdade de
Medicina de São José do Rio Preto, Brazil
Note: [] Corresponding author: C. B. Santos-Rebouças, PhD.,
Serviço de Genética Humana, Departamento de Genética, Instituto de
Biologia Roberto Alcantara Gomes, Universidade do Estado do Rio de Janeiro, Rua
São Francisco Xavier, 524, PHLC – sala 501, Maracanã 20550-013, Rio de
Janeiro, RJ, Brazil. Tel.: +55 21 25877567; Fax: +55 21 25877377; E-mail:
cbs@alternex.com.br
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.
