Journal
NEUROBIOLOGY OF AGING
Volume 27, Issue 4, Pages 614-623Publisher
ELSEVIER SCIENCE INC
DOI: 10.1016/j.neurobiolaging.2005.03.014
Keywords
Alzheimer's disease; phosphatidylethanolamine binding protein; A beta amyloid; amyloid precursor protein; hippocampus; transgenic mouse; Tg2576
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Phosphatidylethanolamine binding protein (PEBP) is a multifunctional protein, with proposed roles as the precursor protein of hippocampal cholinergic neurostimulating peptide (HCNP), and as the Raf kinase inhibitor protein (RKIP). Previous studies have demonstrated a decrease in PEBP mRNA in CA1 region of AD hippocampus. The current study demonstrates that PEBP is decreased in the hippocampus of 11 month Tg2576 mice, in the absence of change in mRNA levels compared to non-transgenic littermates. The level of PEBP in transgenic mouse hippocampus significantly decreases at 11 months (a time point when A beta begins accumulating) and 15 months (when A beta plaques have formed). There was a significant correlation between decreased PEBP expression and accumulation of A beta. Immunohistochemical studies on Tg2576 and AD brain sections demonstrate that PEBP immunoreactivities are present at the periphery of dense multicore A beta plaques, and in selective astrocytes, primarily surrounding plaques. These findings suggest that PEBP expression may be influenced by accumulation of A beta. Down-regulation of PEBP may result in lower levels of HCNP or altered coordination of signal transduction pathways that may contribute to neuronal dysfunction and pathogenesis in AD. (C) 2005 Elsevier Inc. All rights reserved.
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