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P3‐182: Examining the link between synaptosomal accumulation of tau protein and cognitive dysfunction
Author(s) -
Sahara Naruhiko,
Kang Dongcheul,
Yamashita Shunji,
Kimura Tatsuya,
Takashima Akihiko,
Lewis Jada
Publication year - 2009
Publication title -
alzheimer's and dementia
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 6.713
H-Index - 118
eISSN - 1552-5279
pISSN - 1552-5260
DOI - 10.1016/j.jalz.2009.04.1056
Subject(s) - tauopathy , tau protein , genetically modified mouse , neuroscience , extracellular , transgene , biology , dementia , intracellular , psychology , microbiology and biotechnology , chemistry , endocrinology , medicine , alzheimer's disease , neurodegeneration , biochemistry , disease , gene
leading to restrictions of transport and promotion of amyloid plaques. Moreover, dendritic abnormalities like spine loss, shaft atrophy, bending, abrupt branch ending, varicosity formation, and sprouting are evoked. Methods: As a suitable transgenic model for Alzheimer’s disease, 3xTg-AD mice develop both beta amyloid (Aß) and tangle pathology, providing the opportunity to study degenerative processes resembling human AD-pathology. After crossing 3xTg-AD mice with a mouse line expressing yellow fluorescent protein in cortical and hippocampal neurons (YFP-H mice), we were able to perform 2-photon in vivo imaging of neurites down to the level of single dendritic spines. Investigating tau-dependent loss of spines in the somatosensory cortex, we found dendritic dystrophies which differed significantly from previously described degenerative neuritic changes: The dendritic swellings showed a distinct morphology resembling a pearl necklace and were positively stained for hyperphosphorylated tau as well as Aß. Huge varicosities surrounded a YFP-negative vacuole-like centre. In degenerative hippocampal neurites on the contrary, dystrophies near amyloid plaques contained neither hyperphosphorylated tau nor Aß, were YFP-positive throughout, and of rather spherical shape without visible interconnection. Results: By means of electron microscopy we analyzed the ultrastructural composition of the observed neuritic swellings, answering the following questions: What is inside the cortical dendritic swellings? What does their YFP-negative centre consist of? Is there an axodendritic shift of tau like in AD? Are the observed dystrophic changes specific for dendrites or also found in axons? How do cortical and hippocampal neuritic varicosities differ on the ultrastructural level? Conclusions: Our studies contribute to a better understanding of tau-dependent dendropathy in 3xTg-AD mice and may also help to elucidate the cause of neuritic dystrophies in AD.