title: Clinical and pathological characteristics of LRRK2 G2019S patients with PD.
abstract: The objective of this study is to describe the neuropathologic findings in three LRRK2 G2019S carriers with Parkinson's disease (PD). We cross-referenced a list of 956 PD individuals that had been previously genotyped in clinical studies at Columbia University, with 282 subjects with a parkinsonian syndrome who came to autopsy in our brain bank since 1991. We found three autopsies of G2019S mutation carriers. Pathological analyses of the samples were blind to the genetic findings. We retrospectively reviewed the clinical records of the three patients. All three had a clinical and pathological diagnosis of PD. Cognitive impairment was a late feature in two out of three patients. Cortical involvement varied significantly: one had diffuse Lewy body (LB) pathology, tau inclusions, and amyloid pathology consistent with advanced Alzheimer's disease; one had diffuse cortical LB; and one had only brainstem predominant LB pathology. Cognitive impairment may be a long-term complication in G2019S mutation carriers. However, the extent of cortical involvement is variable. Larger longitudinal follow-up of LRRK2 G2019S mutation carriers is required to assess for risk factors for cortical involvement and dementia.
authors.affiliation: Department of Neurology, College of Physicians and Surgeons, Columbia University, New York, NY, USA.
authors.forename: Markos
authors.initials: M
authors.lastname: Poulopoulos
authors.forename: Etty
authors.initials: E
authors.lastname: Cortes
authors.forename: Jean-Paul G
authors.initials: JP
authors.lastname: Vonsattel
authors.forename: Stanley
authors.initials: S
authors.lastname: Fahn
authors.forename: Cheryl
authors.initials: C
authors.lastname: Waters
authors.forename: Lucien J
authors.initials: LJ
authors.lastname: Cote
authors.forename: Carol
authors.initials: C
authors.lastname: Moskowitz
authors.forename: Lawrence S
authors.initials: LS
authors.lastname: Honig
authors.forename: Lorraine N
authors.initials: LN
authors.lastname: Clark
authors.forename: Karen S
authors.initials: KS
authors.lastname: Marder
authors.forename: Roy N
authors.initials: RN
authors.lastname: Alcalay
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D000544:Alzheimer Disease / Q000235:genetics / Q000473:pathology; D005260:Female; D005838:Genotype; D006801:Humans; D000071158:Leucine-Rich Repeat Serine-Threonine Protein Kinase-2; D020961:Lewy Body Disease / Q000235:genetics / Q000473:pathology; D008297:Male; D010300:Parkinson Disease / Q000235:genetics* / Q000473:pathology*; D017354:Point Mutation / Q000235:genetics*; D017346:Protein Serine-Threonine Kinases / Q000235:genetics*; D012189:Retrospective Studies; D012307:Risk Factors
chemical_list: C495280:LRRK2 protein, human; D000071158:Leucine-Rich Repeat Serine-Threonine Protein Kinase-2; D017346:Protein Serine-Threonine Kinases