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Neurology 2000;54:1099-1102
© 2000 American Academy of Neurology
Articles

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

M. Otto, MD, H. Esselmann, PhD, W. Schulz-Schaeffer, MD, M. Neumann, MD, A. Schröter, MD, P. Ratzka, MD, L. Cepek, MD, I. Zerr, MD, P. Steinacker, PhD, O. Windl, PhD, J. Kornhuber, MD, H. A. Kretzschmar, MD, S. Poser, MD and J. Wiltfang, MD

From the Neurologische Klinik und Poliklinik (Drs. Otto, Schrôter, Ratzka, Cepek, Zerr, Steinacker, and Poser) and Psychiatrische Klinik und Poliklinik (Drs. Esselmann, Kornhuber, and Wiltfang), Institut für Neuropathologie (Drs. Schulz-Schaeffer, Neumann, Windl, and Kretzschmar), Georg-August-Universität Göttingen, Germany.

Address correspondence and reprint requests to Dr. Markus Otto, Neurologische Klinik und Poliklinik, Universität Göttingen, Robert-Koch Str. 40, 37070 Göttingen, Germany; e-mail: motto{at}gwdg.de

OBJECTIVES: Decreased levels of Aß1-42 are found in CSF of patients with AD. Because early stages of Creutzfeldt-Jakob disease (CJD) and AD share several clinical features, we investigated Aß1-42 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 Aß1-42 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 ß-amyloid plaques were seen. Additionally, APOE status was determined in patients with CJD.

RESULTS: Levels of Aß1-42 in CSF were decreased in patients with AD as well as in CJD. Levels of Aß1-42 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 Aß1-42 did not correlate with the APOE {epsilon}4 load in patients with CJD.

CONCLUSION: Low levels of Aß1-42 in CSF do not exclude a diagnosis of CJD. Decreased levels of Aß1-42 in CSF can occur without ß-amyloid plaque formation in the brain. However, the underlying mechanism of this phenomenon must be elucidated.

Key words: Creutzfeldt-Jakob disease—AD—Aß1-42—APOE allele—Protein 14-3-3—Amyloid beta—Laboratory diagnosis.




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