Decreased β-amyloid1-42 in cerebrospinal fluid of patients with Creutzfeldt-Jakob disease

Objectives: Decreased levels of A beta(1-42) are found in CSF of patients with AD. Because early stages of Creutzfeldt-Jakob disease (CJD) and AD share several clinical features, we investigated A beta(1-42) levels in CSF of these groups, inferring that this might give additional help in differentiating patients with CJD from AD patients. Methods: We investigated 27 patients with CJD, 14 patients with AD, 19 patients with other dementias, and 20 nondemented controls (NDC) for A beta(1-42) in CSF. Twenty-four of the 27 CJD patients were neuropathologically verified. All the neuropathologically verified patients presented with a type 1 prion protein pattern. CJD patients were all homozygous for methionine at codon 129. Except in five CJD patients, no beta-amyloid plaques were seen. Additionally, APOE status was determined in patients with CJD. Results: Levels of A beta(1-42) in CSF were decreased in patients with AD as well as in CJD. Levels of A beta(1-42) in CSF of patients with CJD and AD were significantly different from the other dementia and NDC groups. There was no substantial difference between the CJD and AD groups (p = 0.66). Decreased levels of A beta(1-42) did not correlate with the APOE epsilon 4 load in patients with CJD. Conclusion: Low levels of A beta(1-42) in CSF do not exclude a diagnosis of CJD. Decreased levels of A beta(1-42) in CSF can occur without p-amyloid plaque formation in the brain. However, the underlying mechanism of this phenomenon must be elucidated.