title: 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.affiliation: Uppsala University, Department of Public Health/Geriatrics, Uppsala Science Park, Uppsala, Sweden. johan.sundelof@pubcare.uu.se
authors.forename: J
authors.initials: J
authors.lastname: Sundelöf
authors.forename: J
authors.initials: J
authors.lastname: Arnlöv
authors.forename: E
authors.initials: E
authors.lastname: Ingelsson
authors.forename: J
authors.initials: J
authors.lastname: Sundström
authors.forename: S
authors.initials: S
authors.lastname: Basu
authors.forename: B
authors.initials: B
authors.lastname: Zethelius
authors.forename: A
authors.initials: A
authors.lastname: Larsson
authors.forename: M C
authors.initials: MC
authors.lastname: Irizarry
authors.forename: V
authors.initials: V
authors.lastname: Giedraitis
authors.forename: E
authors.initials: E
authors.lastname: Rönnemaa
authors.forename: M
authors.initials: M
authors.lastname: Degerman-Gunnarsson
authors.forename: B T
authors.initials: BT
authors.lastname: Hyman
authors.forename: H
authors.initials: H
authors.lastname: Basun
authors.forename: L
authors.initials: L
authors.lastname: Kilander
authors.forename: L
authors.initials: L
authors.lastname: Lannfelt
mesh_terms: D000368:Aged; D000375:Aging / Q000097:blood*; D000544:Alzheimer Disease / Q000097:blood* / Q000453:epidemiology* / Q000503:physiopathology; D015415:Biomarkers / Q000032:analysis / Q000097:blood; D001921:Brain / Q000378:metabolism / Q000503:physiopathology; D015984:Causality; D015331:Cohort Studies; D055316:Cystatin C; D015891:Cystatins / Q000032:analysis / Q000097:blood*; D019610:Cytoprotection / Q000502:physiology*; D015536:Down-Regulation / Q000502:physiology; D006801:Humans; D006949:Hyperlipidemias / Q000453:epidemiology; D007674:Kidney Diseases / Q000453:epidemiology; D008137:Longitudinal Studies; D008297:Male; D009765:Obesity / Q000453:epidemiology; D011237:Predictive Value of Tests; D016016:Proportional Hazards Models; D012307:Risk Factors; D012907:Smoking / Q000453:epidemiology; D013548:Sweden / Q000453:epidemiology
chemical_list: D015415:Biomarkers; C525030:CST3 protein, human; D055316:Cystatin C; D015891:Cystatins