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Review
. 2021 Jan 28:15:634666.
doi: 10.3389/fnins.2021.634666. eCollection 2021.

Inflammatory Diseases Among Norwegian LRRK2 Mutation Carriers. A 15-Years Follow-Up of a Cohort

Jan O Aasly  1   2
Affiliations
Review

Inflammatory Diseases Among Norwegian LRRK2 Mutation Carriers. A 15-Years Follow-Up of a Cohort

Jan O Aasly. Front Neurosci. .

Abstract

The first families with LRRK2 related Parkinson's disease (PD) were presented around 15 years ago and numerous papers have described the characteristics of the LRRK2 phenotype. The prevalence of autosomal dominant PD varies around the world mainly depending on local founder effects. The highest prevalence of LRRK2 G2019S PD in Norway is located to the central part of the country and most families could be traced back to common ancestors. The typical Norwegian LRRK2 phenotype is not different from classical PD and similar to that seen in most other LRRK2 families. The discovery of LRRK2 PD has allowed us to follow-up multi-incident families and to study their phenotype longitudinally. In the Norwegian LRRK2 families there has been a significantly higher incidence of inflammatory diseases like multiple sclerosis and rheumatoid arthritis that seen in other PD populations. Recent studies in LRRK2 mechanisms have indicated that this protein may be crucial in initiating disease processes. In this short survey of 100 Norwegian mutation carriers followed through more than 15 years are presented. The prevalence of inflammatory diseases among these cases is highlighted. The role of LRRK2 in the conversion process from carrier status to PD phenotype is still unknown and disease generating mechanisms important for initiating LRRK2 PD are still to be identified.

Keywords: LRRK2; Parkinson’s disease; achalasia; dementia; inflammation; multiple sclerosis; rheumatoid arthritis.

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Conflict of interest statement

The author declares that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.

Figures

FIGURE 1
FIGURE 1
First identified Norwegian LRRK2 patients, family photo 1911 (with permissions from the family).
FIGURE 2
FIGURE 2
Case 4, achalasia, a barium esophagogram showing a narrowed part of the lower part of the esophagus.
FIGURE 3
FIGURE 3
Case 4, Datscan at age 67 years. Bradykinesia and rigidity but no tremor.
FIGURE 4
FIGURE 4
Case 3, LRRK2 mutation carrier, severe MS. MRI at age 50 with white matter lesions and some central and cortical brain atrophy.
FIGURE 5
FIGURE 5
Case 6, 65 years-old healthy LRRK2 mutation carrier with sero-positive rheumatoid arthritis. PET-scan at age 50 DAT 11C-MP, methylphenidate. Left scan: Case 6, at age 50, right scan: 54 years-old normal control (with permission from J Stoessl and V Sossi, Pacific Parkinson’s Research Centre, Vancouver, British Columbia, Canada).
See this image and copyright information in PMC

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