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Mol Med. 2000 May;6(5):430-9.

Elevated A beta and apolipoprotein E in A betaPP transgenic mice and its relationship to amyloid accumulation in Alzheimer's disease.

Author information

1
Haldeman Laboratory for Alzheimer Disease Research, Sun Health Research Institute, Sun City, Arizona 85351, USA.

Abstract

BACKGROUND:

Amyloid-beta (A beta) accumulates in plaques and as cerebral amyloid angiopathy (CAA) in the brains of both Alzheimer's disease (AD) patients and transgenic A betaPPswe/tg2576 (tg2576) mice. Increasingly, evidence in humans and mice shows this process to be modulated by apolipoprotein E (apoE).

MATERIALS AND METHODS:

To explore this relationship, we measured apoE and A beta levels in brains of tg2576 mice and controls at intervals between 2 and 20 months. In addition, A beta concentrations in plasma and muscle of these animals were also quantified.

RESULTS:

Quite strikingly, we found that the amount of tg2576 mice brain apoE was elevated by an average of 45%, relative to the control mice from 2 months on. The level of brain apoE soared after 14 months to almost 60% greater than the level found in control mice. A beta concentrations in brains before 9 months were less than 2 ng/mg of protein, but by 14 months concentrations rose to 8.7 ng/mg, and by 20 months to 47 ng/mg. In plasma, we noted that the levels of A beta in tg2576 mice declined from above 30 ng/ml prior to 12 months to 14 ng/ml by 14 months. Histology showed that A beta plaques and CAA began to be discernible in the tg2576 mice at about 9 and 20 months of age, respectively.

CONCLUSIONS:

ApoE was immunocytochemically detected in neuritic plaques that were positive for thioflavine-S. We suggest that the elevation of brain apoE in tg2576 mice participates in an age-related dysregulation of A beta clearance and signals the start of A beta sequestration during the time of cognitive dysfunction.

PMID:
10952022
PMCID:
PMC1949958
[Indexed for MEDLINE]
Free PMC Article

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