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LRRK2 variant associated with Alzheimer's disease
1Department of Neurology, Clinical Research and Health Screening, Singapore General Hospital, Singapore.
Neurobiology of Aging
|December 19, 2009
Summary
The leucine-rich repeat kinase-2 (LRRK2) R1628P variant is linked to increased Alzheimer's disease (AD) risk. This genetic factor may promote cell death, suggesting a role in AD pathogenesis.
Area of Science:
- Neurogenetics
- Neurodegenerative Diseases
- Molecular Biology
Background:
- Parkinson's disease (PD) patients with leucine-rich repeat kinase-2 (LRRK2) mutations can exhibit overlapping neurodegenerative pathologies, including Alzheimer's disease (AD).
- Investigating specific LRRK2 variants may elucidate shared mechanisms in neurodegeneration.
Purpose of the Study:
- To investigate the association between the LRRK2 R1628P risk variant and Alzheimer's disease (AD).
- To explore the functional impact of the LRRK2 R1628P variant on cellular apoptosis and cell death.
Main Methods:
- Genotyping analysis of the LRRK2 R1628P variant in 885 subjects (AD patients and controls).
- In vitro studies using human cell lines transfected with R1628P variant compared to wild-type LRRK2 to assess apoptosis and cell death rates.
Main Results:
- The R1628P allele frequency was significantly higher in AD patients (3.5%) compared to controls (1.6%) (OR 2.3, p=0.018).
- In vitro, LRRK2 R1628P transfected cell lines showed increased percentages of apoptosis and cell death compared to wild-type LRRK2 (p<0.05).
Conclusions:
- The LRRK2 R1628P variant is associated with an increased risk of Alzheimer's disease in the studied population.
- In vitro evidence suggests the LRRK2 R1628P variant is functional and may predispose cells to apoptosis, contributing to AD pathogenesis.
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