RGD Reference Report - Serum cystatin C and the risk of Alzheimer disease in elderly men. - Rat Genome Database

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

Authors: Sundelof, J  Arnlov, J  Ingelsson, E  Sundstrom, J  Basu, S  Zethelius, B  Larsson, A  Irizarry, MC  Giedraitis, V  Ronnemaa, E  Degerman-Gunnarsson, M  Hyman, BT  Basun, H  Kilander, L  Lannfelt, L 
Citation: Sundelof J, etal., Neurology. 2008 Sep 30;71(14):1072-9.
RGD ID: 2314333
Pubmed: PMID:18824671   (View Abstract at PubMed)
PMCID: PMC2676985   (View Article at PubMed Central)
DOI: DOI:10.1212/01.wnl.0000326894.40353.93   (Journal Full-text)

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.

RGD Manual Disease Annotations    Click to see Annotation Detail View
TermQualifierEvidenceWithReferenceNotesSourceOriginal Reference(s)
Alzheimer's disease susceptibilityIEP 2314333protein:decreased expression:serum (human)RGD 
Alzheimer's disease susceptibilityISOCST3 (Homo sapiens)2314333; 2314333protein:decreased expression:serum (human)RGD 

Objects Annotated

Genes (Rattus norvegicus)
Cst3  (cystatin C)

Genes (Mus musculus)
Cst3  (cystatin C)

Genes (Homo sapiens)
CST3  (cystatin C)


Additional Information