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

Abstract

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.

• Authors: 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
• Journal: Neurology (Neurology) Vol. 71 Issue 14 Pg. 1072-9 (Sep 30 2008) ISSN: 1526-632X [Electronic] United States
• PMID: 18824671 (Publication Type: Journal Article, Research Support, N.I.H., Extramural, Research Support, Non-U.S. Gov't)

Chemical References

• Biomarkers
• CST3 protein, human
• Cystatin C
• Cystatins

Topics

• Aged
• Aging (blood)
• Alzheimer Disease (blood, epidemiology, physiopathology)
• Biomarkers (analysis, blood)
• Brain (metabolism, physiopathology)
• Causality
• Cohort Studies
• Cystatin C
• Cystatins (analysis, blood)
• Cytoprotection (physiology)
• Down-Regulation (physiology)
• Humans
• Hyperlipidemias (epidemiology)
• Kidney Diseases (epidemiology)
• Longitudinal Studies
• Male
• Obesity (epidemiology)
• Predictive Value of Tests
• Proportional Hazards Models
• Risk Factors
• Smoking (epidemiology)
• Sweden (epidemiology)