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| Secreted amyloid beta-protein similar to that in the senile plaques of Alzheimer's disease is increased in vivo by the presenilin 1 and 2 and APP mutations linked to familial Alzheimer's disease |
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| Author(s): Scheuner D, Eckman C, Jensen M, Song X, Citron M, Suzuki N, Bird TD, Hardy J, Hutton M, Kukull W, Larson E, LevyLahad E, Viitanen M, Peskind E, Poorkaj P, Schellenberg G, Tanzi R, Wasco W, Lannfelt L, Selkoe D, Younkin S |
| Source: NATURE MEDICINE Volume: 2 Issue: 8 Pages: 864-870 Published: AUG 1996 |
| Times Cited: 1,352 References: 40 |
| Abstract: To determine whether the presenilin 1 (PS1), presenilin 2 (PS2) and amyloid beta-protein precursor (APP) mutations linked to familial Alzheimer's disease (FAD) increase the extracellular concentration of amyloid beta-protein (A beta) ending at A beta 42(43) in vivo, we performed a blinded comparison of plasma A beta levels in carriers of these mutations and controls. A beta 1-42(43) was elevated in plasma from subjects with FAD-linked PS1 (P < 0.0007), PS2(N141I) (P = 0.009), APP(K670N,M671L) (P < 0.0001), and APP(Y717I) (one subject) mutations. A beta ending at A beta 42(43) was also significantly elevated in fibroblast media from subjects with PS1 (P < 0.0001) or PS2 (P = 0.03) mutations. These findings indicate that the FAD-linked mutations may all cause Alzheimer's disease by increasing the extracellular concentration of A beta 42(43), thereby fostering cerebral deposition of this highly amyloidogenic peptide. |
| Document Type: Article |
| Language: English |
Addresses:
1. CASE WESTERN RESERVE UNIV, DEPT NEUROSCI, CLEVELAND, OH 44106 USA
2. MAYO CLIN JACKSONVILLE, JACKSONVILLE, FL 32224 USA
3. HUDDINGE UNIV HOSP, KAROLINSKA INST, DEPT CLIN NEUROSCI & FAMILY MED, NOVUM KFC, S-14186 HUDDINGE, SWEDEN
4. CASE WESTERN RESERVE UNIV, DEPT PATHOL, CLEVELAND, OH 44106 USA
5. HARVARD UNIV, SCH MED, CTR NEUROL DIS, BOSTON, MA 02115 USA
6. BRIGHAM & WOMENS HOSP, BOSTON, MA 02115 USA
7. TAKEDA CHEM IND LTD, DIV DISCOVERY RES, TSUKUBA, IBARAKI 30042 JAPAN
8. UNIV WASHINGTON, DEPT NEUROL, SEATTLE, WA 98185 USA
9. UNIV WASHINGTON, DEPT EPIDEMIOL, SEATTLE, WA 98185 USA
10. UNIV WASHINGTON, DEPT MED, SEATTLE, WA 98185 USA
11. UNIV WASHINGTON, DEPT PSYCHIAT & BEHAV SCI, SEATTLE, WA 98185 USA
12. UNIV WASHINGTON, DEPT PHARMACOL, SEATTLE, WA 98185 USA
13. VET AFFAIRS PUGET SOUND HLTH CARE SYST, NEUROL SERV, SEATTLE, WA 98108 USA
14. VET AFFAIRS PUGET SOUND HLTH CARE SYST, CTR GERIATR RES EDUC & CLIN, SEATTLE, WA 98108 USA
15. UNIV S FLORIDA, DEPT PSYCHIAT, SUNCOAST ALZHEIMERS DIS LABS, TAMPA, FL 33613 USA
16. HARVARD UNIV, SCH MED, MASSACHUSETTS GEN HOSP, DEPT NEUROL, GENET & AGING UNIT, CHARLESTOWN, MA 02129 USA |
| Publisher: NATURE PUBLISHING CO, 345 PARK AVE SOUTH, NEW YORK, NY 10010-1707 |
| Subject Category: Biochemistry & Molecular Biology; Cell Biology; Medicine, Research & Experimental |
| IDS Number: UZ804 |
| ISSN: 1078-8956 |
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