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APOE 4 allele is associated with reduced cerebrospinal fluid levels of Aß42

From the Center for Genomics and Bioinformatics (Dr. Prince), Karolinska Institute, Stockholm, Department of Clinical Chemistry and Transfusion Medicine (Drs. Zetterberg and Blennow), Sahlgrenska University Hospital, Göteborg University, Karolinska Institute (Dr. Andreasen), Neurotec, Huddinge University Hospital, Department of Geriatric Medicine (Dr. Marcusson), Linköping University Hospital, and Institute of Clinical Neuroscience (Dr. Blennow), Department of Experimental Neuroscience, Sahlgrenska University Hospital, Göteborg University, Mölndal, Sweden.

Address correspondence and reprint requests to Dr. H. Zetterberg, Department of Clinical Chemistry and Transfusion Medicine, Sahlgrenska University Hospital, Göteborg University, S-413 45 Gothenburg, Sweden; e-mail: henrik.zetterberg{at}clinchem.gu.se

The 4 allele of APOE is a risk factor for Alzheimer disease (AD). By analysis of a large cohort of AD patients (n = 563) and control subjects (n = 118), it is shown that the 4 allele is strongly associated with reduced CSF levels of ß-amyloid (1–42) (Aß42) in both AD (p < 10^–9) and control (p = 0.0012) populations. As no associations of APOE variants with other indexes of AD severity were observed, this effect may reflect a fundamental involvement of ApoE in Aß metabolism.

Received December 3, 2003. Accepted in final form January 26, 2004.

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