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| Sequence of deposition of heterogeneous amyloid beta-peptides and APO E in Down syndrome: Implications for initial events in amyloid plaque formation |
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| Author(s): Lemere CA, Blusztajn JK, Yamaguchi H, Wisniewski T, Saido TC, Selkoe DJ |
| Source: NEUROBIOLOGY OF DISEASE Volume: 3 Issue: 1 Pages: 16-32 Published: FEB 1996 |
| Times Cited: 214 References: 50 |
| Abstract: Patients with trisomy 21 [Down syndrome (DS)] progressively develop amyloid beta-protein (A beta) deposits and then other features of Alzheimer's disease (AD), apparently due to increased gene dosage and thus expression of the beta-amyloid precursor protein, Because the neuropathological phenotype in older DS subjects closely resembles that of AD, the examination of DS brains of increasing age provides a unique model of the progression of AD. Here, we characterized the deposition of several A beta peptides and apolipoprotein E in formalin-fixed brain sections from 29 DS subjects between 3 and 73 years old, Amyloid plaque number and the percentage of cortical area they occupied were quantified by computerized image analysis. A beta ending at amino acid 42 (A beta(42)) was the earliest form of A beta deposited in DS cortex, It was observed in 7 of 16 young (3-30 years) subjects, with the earliest deposition occurring at age 12. A beta ending at residue 40 (A beta(40)) was not detected until similar to age 30, a time when degenerating neurites around A beta immunoreactive (IR) plaques were first observed, and the frequency of A beta(40) IR plaques then rose with age, Even in old (51-73 years) DS subjects, A beta(42) IR plaques were always more abundant than A beta(40) IR plaques, A beta peptides starting at aspartate 1 or pyroglutamate 3 were detected in small subsets of compacted, neuritic plaques beginning around age 30 and rose with age, the latter species always exceeding the former, Thus, the N-termini of the A beta(42) peptides abundantly deposited in very young DS subjects remain unknown, Apo E was detectable in a small subset of A beta(42) in plaques beginning at age 12 and rose steadily with age; it clearly followed the deposition of A beta. Our analysis of very young DS brains suggests that amyloid plaque formation begins with A beta(42)-ending peptides, and the number and percentage of cortical area of A beta(42) plaques increase very little with advancing age, while other heterogeneous A beta species and Apo E progressively accrue onto plaques containing A beta(42). (C) 1996 Academic Press, Inc. |
| Document Type: Article |
| Language: English |
Addresses:
1. HARVARD UNIV, BRIGHAM & WOMENS HOSP, SCH MED, CTR NEUROL DIS, BOSTON, MA 02115 USA
2. BOSTON UNIV, SCH MED, DEPT PATHOL, BOSTON, MA 02215 USA
3. GUNMA UNIV, COLL MED CARE & TECHNOL, GUNMA, JAPAN
4. NYU, MED CTR, DEPT NEUROL, NEW YORK, NY 10012 USA
5. TOKYO METROPOLITAN INST MED SCI, DEPT MOL BIOL, TOKYO 113, JAPAN |
| Publisher: ACADEMIC PRESS INC JNL-COMP SUBSCRIPTIONS, 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 |
| Subject Category: Neurosciences |
| IDS Number: VU960 |
| ISSN: 0969-9961 |
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