학술논문

Synaptic and metabolic gene expression alterations in neurons that are recipients of proteopathic tau seeds
Document Type
article
Source
Acta Neuropathologica Communications, Vol 8, Iss 1, Pp 1-10 (2020)
Subject
Alzheimer’s disease
Neurofibrillary tangles
Tau seeding
RNA expression
Neurology. Diseases of the nervous system
RC346-429
Language
English
ISSN
2051-5960
Abstract
Abstract Recent studies suggest that misfolded tau molecules can be released, and taken up by adjacent neurons, propagating proteopathic seeds across neural systems. Yet critical to understanding whether tau propagation is relevant in pathophysiology of disease would be to learn if it alters neuronal properties. We utilized high resolution multi-color in situ hybridization technology, RNAScope, in a well-established tau transgenic animal, and found that a subset of neurons in the cortex do not appear to express the transgene, but do develop phospho-tau positive inclusions, consistent with having received tau seeds. Recipient neurons show decreases in their expression of synaptophysin, CAMKIIα, and mouse tau in both young and old animals. These results contrast with neurons that develop tau aggregates and also overexpress the transgene, which have few changes in expression of metabolic and synaptic markers. Taken together, these results strongly suggest that tau propagation impacts neuronal functional integrity.