Journal of neural transmission
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Despite extensive research over the last decades the clinical significance of white matter lesions (WMLs) is still a matter of debate. Here, we review current knowledge of the correlation between WMLs and cognitive functioning as well as their predictive value for future stroke, dementia, and functional decline in activities of daily living. ⋯ One reason for the variability of the relationship between WMLs and clinic on an individual level is probably the complexity of the association. Numerous factors such as cognitive reserve, concomitant loss of brain volume, and ultrastructural changes have been identified as mediators between white matter damage and clinical findings, and need to be incorporated in the consideration of WMLs as visible markers of these detrimental processes.
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Sequence variants at or near the leucine-rich repeat kinase 2 (LRRK2) locus have been associated with susceptibility to three human conditions: Parkinson's disease (PD), Crohn's disease and leprosy. As all three disorders represent complex diseases with evidence of inflammation, we hypothesized a role for LRRK2 in immune cell functions. Here, we report that full-length Lrrk2 is a relatively common constituent of human peripheral blood mononuclear cells (PBMC) including affinity isolated, CD14(+) monocytes, CD19(+) B cells, and CD4(+) as well as CD8(+) T cells. ⋯ In the same cells, lrrk2 appears to co-regulate autophagy. A pattern recognition receptor-type function for LRRK2 could explain its locus' association with Crohn's disease and leprosy risk. We speculate that the role of Lrrk2 in immune cells may also be relevant to the susceptibility of developing PD or its progression.