| Autor: |
Takahashi RH; Department of Neurology and Neuroscience, Weill Medical College of Cornell University, New York, New York 10021, USA., Milner TA, Li F, Nam EE, Edgar MA, Yamaguchi H, Beal MF, Xu H, Greengard P, Gouras GK |
| Jazyk: |
angličtina |
| Zdroj: |
The American journal of pathology [Am J Pathol] 2002 Nov; Vol. 161 (5), pp. 1869-79. |
| DOI: |
10.1016/s0002-9440(10)64463-x |
| Abstrakt: |
A central question in Alzheimer's disease concerns the mechanism by which beta-amyloid contributes to neuropathology, and in particular whether intracellular versus extracellular beta-amyloid plays a critical role. Alzheimer transgenic mouse studies demonstrate brain dysfunction, as beta-amyloid levels rise, months before the appearance of beta-amyloid plaques. We have now used immunoelectron microscopy to determine the subcellular site of neuronal beta-amyloid in normal and Alzheimer brains, and in brains from Alzheimer transgenic mice. We report that beta-amyloid 42 localized predominantly to multivesicular bodies of neurons in normal mouse, rat, and human brain. In transgenic mice and human Alzheimer brain, intraneuronal beta-amyloid 42 increased with aging and beta-amyloid 42 accumulated in multivesicular bodies within presynaptic and especially postsynaptic compartments. This accumulation was associated with abnormal synaptic morphology, before beta-amyloid plaque pathology, suggesting that intracellular accumulation of beta-amyloid plays a crucial role in Alzheimer's disease. |
| Databáze: |
MEDLINE |
| Externí odkaz: |
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