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| Isoform-specific modulation by apolipoprotein E of the activities of secreted beta-amyloid precursor protein |
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| Author(s): Barger SW, Mattson MP |
| Source: JOURNAL OF NEUROCHEMISTRY Volume: 69 Issue: 1 Pages: 60-67 Published: JUL 1997 |
| Times Cited: 38 References: 43 |
| Abstract: The genes for both the beta-amyloid precursor protein and apolipoprotein E (ApoE) have been linked to Alzheimer's disease. This connection suggests the possibility that these proteins interact physically or functionally. To explore this idea, we focused on the neuroprotective activity of secreted amyloid precursor protein (sAPP) and related signal transduction events. After coincubation with ApoE, sAPP exhibited an enhanced [Ca2+](i)-lowering activity and enhanced protection against excitotoxicity in rat primary hippocampal neurons. In contrast, the stimulation of phosphoinositide production by sAPP was inhibited by ApoE. Kinetic analyses and coimmunoprecipitation experiments indicated that these actions result from formation of a heteromeric complex between ApoE and sAPP. Furthermore, the ApoE4 isoform, which seems to accelerate the onset of Alzheimer's disease, was less potent than ApoE3 in modifying each activity of sAPP. These data suggest that sAPP-dependent neuroprotective mechanisms would be compromised in individuals expressing ApoE4, a scenario that may contribute to the development of Alzheimer's disease. |
| Document Type: Article |
| Language: English |
| Reprint Address: Barger, SW (reprint author), JOHN L MCCLELLAN MEM VET ADM MED CTR, RES SERV 151, CTR GERIATR RES EDUC & CLIN, 4300 W 7TH ST, LITTLE ROCK, AR 72205 USA |
Addresses:
1. UNIV ARKANSAS MED SCI HOSP, DONALD W REYNOLDS DEPT GERIATR, LITTLE ROCK, AR 72205 USA
2. UNIV ARKANSAS MED SCI HOSP, DEPT ANAT, LITTLE ROCK, AR 72205 USA
3. UNIV KENTUCKY, SANDERS BROWN CTR AGING, LEXINGTON, KY 40536 USA
4. UNIV KENTUCKY, DEPT ANAT & NEUROBIOL, LEXINGTON, KY 40536 USA |
| Publisher: LIPPINCOTT-RAVEN PUBL, 227 EAST WASHINGTON SQ, PHILADELPHIA, PA 19106 |
| Subject Category: Biochemistry & Molecular Biology; Neurosciences |
| IDS Number: XF431 |
| ISSN: 0022-3042 |
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