Association between the LRP1B and APOE loci and the development of Parkinson’s disease dementia

Parkinson’s disease (PD) is one of the most common age-related neurodegenerative disorders. Although predominantly a motor disorder, cognitive impairment and dementia are important features of PD, particularly in the later stages of the disease. However, the rate of cognitive decline varies widely among PD patients, and the genetic basis for this heterogeneity is incompletely understood. Here, we have analysed 3,964 clinically diagnosed PD cases to explore the genetic factors associated with rate of progression to PD dementia. Genome-wide survival analysis identified the APOE- ε4 allele as a major risk factor for the conversion to PD dementia, as well as three new loci , including the ApoE and APP receptor LRP1B. Biomarker analysis also implicates the amyloid pathway in PD dementia, suggesting that amyloid-targeting therapy may have an important role in preventing PDD.