Amyloid is the main pathological substrate of Alzheimer's disease (AD) and has been described in leucine-rich repeat kinase 2 (LRRK2) carriers with Parkinson's disease. LRRK2 has been linked with amyloid precursor protein pathways in neurodegeneration. Two common LRRK2 variants, R1398H and N551K, have been shown to be protective in multiple Parkinson's disease cohorts. We hypothesized that R1398H and N551K may be protective in AD. In a case-control study involving 1390 subjects (719 controls and 671 AD cases), R1398H was demonstrated in 16.8% of AD cases compared to 16.7% in controls (odds ratio = 1.01, 95% confidence interval = 0.76-1.34, p = 0.94), whereas N551K was demonstrated in 17.3% of AD cases compared to 17.2% of controls (odds ratio = 1.00, 95% confidence interval = 0.76-1.32, p = 0.98). Overall, these results suggest that LRRK2 R1398H or N551K variants do not appear to modulate the risk of AD.
Keywords: Alzheimer's disease; Genes; LRRK2; Variants.
Protective Effect of LRRK2 p.R1398H on Risk of Parkinson's Disease Is Independent of MAPT and SNCA VariantsMG Heckman et al. Neurobiol Aging 35 (1), 266.e5-14. PMID 23962496.The best validated susceptibility variants for Parkinson's disease are located in the α-synuclein (SNCA) and microtubule-associated protein tau (MAPT) genes. Recently, a …
Case-control Analysis of LRRK2 Protective Variants in Essential TremorASL Ng et al. Sci Rep 8 (1), 5346. PMID 29593234.Co-existence of Parkinson's disease (PD) and essential tremor (ET) may reflect overlapping pathophysiology underlying both conditions. Furthermore, PD patients with leuci …
LRRK2 Variation and Dementia With Lewy BodiesMG Heckman et al. Parkinsonism Relat Disord 31, 98-103. PMID 27521182.LRRK2 does not appear to play a major role in DLB, however further study of p.G2019S and the p.N551K-R1398H-K1423K haplotype is warranted to better understand their invol …
LRRK2 and NeurodegenerationG Santpere et al. Acta Neuropathol 117 (3), 227-46. PMID 19142648. - ReviewMutations in leucine-rich repeat kinase 2 gene (PARK8/LRRK2) encoding the protein Lrrk2 are causative of inherited and sporadic Parkinson's disease (PD) with phenotypic m …
Caenorhabditis Elegans as an Experimental Tool for the Study of Complex Neurological Diseases: Parkinson's Disease, Alzheimer's Disease and Autism Spectrum DisorderF Calahorro et al. Invert Neurosci 11 (2), 73-83. PMID 22068627. - ReviewThe nematode Caenorhabditis elegans has a very well-defined and genetically tractable nervous system which offers an effective model to explore basic mechanistic pathways …
- Alzheimer Disease / genetics *
- Genetic Association Studies *
- Genetic Variation *
- Leucine-Rich Repeat Serine-Threonine Protein Kinase-2 / genetics *
- Alzheimer Disease / etiology
- Alzheimer Disease / pathology
- Alzheimer Disease / prevention & control
- Amyloid beta-Protein Precursor / metabolism
- Case-Control Studies
- Middle Aged
- Nerve Degeneration / genetics
- Neuroprotection / genetics
- Signal Transduction / genetics
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