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Ultrastructural evidence of fibrillar beta-amyloid associated with neuronal membranes in behaviorally characterized aged dog brains.

Abstract：

:The aged dog brain accumulates beta-amyloid in the form of diffuse senile plaques, which provides a potentially useful in vivo model system for studying the events surrounding the deposition of beta-amyloid. We used postembedding immunocytochemistry at the electron microscopic level to determine the subcellular distribution of beta-amyloid 1-40 and beta-amyloid 1-42 peptides in the prefrontal and parietal cortex of behaviorally characterized dogs ranging in age from one to 17 years. Immunogold particles signaling beta-amyloid 1-42 occurred over intracellular and extracellular fibrils that were approximately 8 nm in width. Intracellular beta-amyloid 1-42 fibrils were found in close proximity to glial fibrillary acidic protein fibers within astrocytes, but only in cells with signs of plasma membrane disruption. Neuronal labeling of beta-amyloid 1-42 appears to be associated with the plasma membrane. Membrane-bound beta-amyloid 1-42 occurs in the form of fine fibrils that are embedded in the dendritic membrane and appear to project into the extracellular space as determined by quantitative analysis of the immunogold particle distribution. Bundles of beta-amyloid 1-42 were also closely associated and/or integrated with degenerating myelin sheaths of axons. In one dog that was impaired on several cognitive tasks, extensive beta-amyloid 1-42 deposition was associated with microvacuolar changes and vascular pathology. The present findings suggest that beta-amyloid 1-42 may be generated at the dendritic plasma membrane as well as in intracellular compartments. The close association between beta-amyloid 1-42 and destroyed myelin suggests one possible new mechanism by which beta-amyloid 1-42 induces neurodegeneration.

journal_name

Neuroscience

journal_title

Neuroscience

authors

Torp R,Head E,Milgram NW,Hahn F,Ottersen OP,Cotman CW

doi

10.1016/s0306-4522(99)00568-0

keywords:

subject

Has Abstract

pub_date

2000-01-01 00:00:00

pages

495-506

issue

3

eissn

0306-4522

issn

1873-7544

pii

S0306-4522(99)00568-0

journal_volume

96

pub_type

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