Affiliations: [a] Center of Neurology, Department of Neurodegeneration and Hertie Institute for Clinical Brain Research, University of Tuebingen, Germany | [b] Department of Geriatric Rehabilitation, Robert-Bosch-Hospital, Stuttgart, Germany | [c] Department of General Neurology, Hertie Institute for Clinical Brain Research, University of Tuebingen, Germany
Correspondence:
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Correspondence to: Walter Maetzler, MD, Department of Neurodegeneration, Hertie Institute for Clinical Brain Research, University of Tuebingen, Hoppe Seyler-Strasse 3, 72076 Tuebingen, Germany. Tel.: +49 7071 2980172; Fax: +49 7071 2944490; E-mail: [email protected].
Note: [1] These authors contributed equally.
Abstract: A large proportion of demented Lewy body disease patients have Alzheimer's disease (AD)- like pathology, in particular amyloid-β (Aβ) plaques. Cystatin C (CysC) is a carrier of soluble Aβ42 in the cerebrospinal fluid (CSF) and reduces Aβ plaque formation. The CST3 BB genotype leads to a reduced secretion of the protein in vitro and increases the risk for AD, suggesting that variability in the CST3 gene and CysC protein concentration may be associated with dementia in Lewy body disease. We therefore determined the CST3 genotype in 51 demented and 71 nondemented Lewy body disease patients, and in 52 controls, as well as CSF CysC and Aβ42 levels from 132 of these subjects. The CST3 BB genotype was associated with lowered CSF CysC levels and with dementia. Demented Lewy body disease patients had decreased CSF CysC levels. The correlation between CSF CysC and Aβ42 levels was high in non-demented subjects, but poor in demented patients. We conclude that, in Lewy body disease, the CST3 BB genotype and low CSF CysC levels are associated with dementia, possibly through a disturbed elimination of soluble Aβ42.
