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.
Sundelöf
J
J
Uppsala University, Department of Public Health/Geriatrics, Uppsala Science Park, Uppsala, Sweden. johan.sundelof@pubcare.uu.se
Arnlöv
J
J
Ingelsson
E
E
Sundström
J
J
Basu
S
S
Zethelius
B
B
Larsson
A
A
Irizarry
M C
MC
Giedraitis
V
V
Rönnemaa
E
E
Degerman-Gunnarsson
M
M
Hyman
B T
BT
Basun
H
H
Kilander
L
L
Lannfelt
L
L
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
D015415:Biomarkers; C525030:CST3 protein, human; D055316:Cystatin C; D015891:Cystatins