Hoffmann, R. A wiki for the life sciences where authorship matters. Nature Genetics (2008)

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Sundelöf, J. et al.

J. Sundelöf, J. Arnlöv, E. Ingelsson, J. Sundström, S. Basu, B. Zethelius, A. Larsson, M.C. Irizarry, V. Giedraitis, E. Rönnemaa, M. Degerman-Gunnarsson, B.T. Hyman, H. Basun, L. Kilander, L. Lannfelt,

Serum cystatin C and the risk of Alzheimer disease in elderly men.

BACKGROUND: Multiple lines of research suggest that increased cystatin C activity in the brain protects against the development of Alzheimer disease (AD). METHODS: Serum cystatin C levels were analyzed at two examinations of the Uppsala Longitudinal Study of Adult Men, a longitudinal, community-based study of elderly men (age 70 years, n = 1,153 and age 77 years, n = 761, a subset of the age 70 examination). Cox regressions were used to examine associations between serum cystatin C and incident AD. AD cases were identified by cognitive screening and comprehensive medical chart review in all subjects. RESULTS: On follow-up (median 11.3 years), 82 subjects developed AD. At age 70 years, lower cystatin C was associated with higher risk of AD independently of age, APOE4 genotype, glomerular filtration rate, diabetes, hypertension, stroke, cholesterol, body mass index, smoking, education level, and plasma amyloid-beta protein 40 and 42 levels (hazard ratio [HR] for lowest [<1.12 micromol/L] vs highest [>1.30 micromol/L] tertile = 2.67, 95% CI 1.22-5.83, p < 0.02). The results were similar at age 77 years (43 participants developed AD during follow-up). Furthermore, a 0.1-mumol/L decrease of cystatin C between ages 70 and 77 years was associated with a 29% higher risk of incident AD (HR 1.29, 95% CI 1.03-1.63, p < 0.03). CONCLUSIONS: Low levels of serum cystatin C precede clinically manifest Alzheimer disease (AD) in elderly men free of dementia at baseline and may be a marker of future risk of AD. These findings strengthen the evidence for a role for cystatin C in the development of clinical AD.[1]

References

Serum cystatin C and the risk of Alzheimer disease in elderly men. Sundelöf, J., Arnlöv, J., Ingelsson, E., Sundström, J., Basu, S., Zethelius, B., Larsson, A., Irizarry, M.C., Giedraitis, V., Rönnemaa, E., Degerman-Gunnarsson, M., Hyman, B.T., Basun, H., Kilander, L., Lannfelt, L. Neurology (2008) [Pubmed]

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