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Decreased α-secretase-cleaved amyloid precursor protein as a diagnostic marker for Alzheimer's diseas

Nature Medicine volume 1, pages 829–832 (1995)Cite this article

Abstract

The neuropathologic hallmarks of Alzheimer's disease (AD) are extracellular plaques and intracellular neurofibrillary tangles. A constituent of senile plaques in AD is β-amyloid, a hydrophobic peptide of 39–43 amino acids1 and a fragment of the amyloid precursor protein (APP). APP can be metabolized by at least two pathways, one of which involves generation of soluble APP by an unidentified enzyme named α-secretase. This cleavage generates α-secretase-cleaved, soluble APP (α–sAPP), which in this investigation was measured by a new assay in cerebrospinal fluid (CSF) from members of a Swedish AD family with a pathogenic mutation at APP670/671 (ref. 2). Family members who carry the mutation and are diagnosed with AD had low levels of α–sAPP (160 ± 48 ng ml−1), with no overlap compared with non-carriers (257 ± 48 ng ml−1). Carriers of the presymptomatic mutation showed intermediate α–sAPP levels. Today there exists no antemortem marker in AD with sufficient sensitivity and specificity, but measurement of α–sAPP represents a new and promising diagnostic marker.

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  1. Lars Lannfelt: Correspondence should be addressed to L.L.

Authors and Affiliations

  1. Karolinska Institute, Department of Clinical Neuroscience (Geriatric Medicine), Huddinge University Hospital, S-141 86, Huddinge, Sweden

    Lars Lannfelt, Hans Basun & Lars-Olof Wahlund

  2. The Salk Institute Biotechnology/Industrial Associates, Inc. (SIBIA), 505 Coast Blvd, South, La Jolla, California, 92037, USA

    Blake A. Rowe & Steven L. Wagner

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  1. Lars Lannfelt
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Lannfelt, L., Basun, H., Wahlund, LO. et al. Decreased α-secretase-cleaved amyloid precursor protein as a diagnostic marker for Alzheimer's diseas. Nat Med 1, 829–832 (1995). https://doi.org/10.1038/nm0895-829

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