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P3‐052: Microvascular changes associated with passive immunotherapy in PDAPP mice: Potential implication for the etiology of vasogenic edema
Author(s) -
Zago Wagner,
Schroeter Sally,
Khan Karen,
Games Dora,
Kinney Gene
Publication year - 2011
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.2011.05.1491
Subject(s) - pathology , perivascular space , immunotherapy , medicine , cerebral amyloid angiopathy , immunohistochemistry , astrocyte , immune system , disease , immunology , central nervous system , dementia
ated protein tau. Clinically AD is characterized by the loss of memory and cognitive decline that can be associated with other symptoms including olfactory alterations. We have produced a transgenic mouse model that develops a tau aggregation similar to that observed in human tauopathies, such as AD. This transgenic mouse line expresses human P301Smutant tau under the control of the Thy 1 promoter. In this mouse line we have investigated the presence of olfactory dysfunction and how this correlates with the presence of tau pathology and cell death in areas of the mouse brain involved in olfaction. Methods: Tau pathology was characterized in P301S tau mouse brain tissue using immunohistochemistry with phosphorylation-independent and phosphorylation-dependent anti-tau antibodies. Neuronal cell death was investigated by immunohistochemistry with anti-neuronal nuclei antibody (NeuN) followed by stereology. Olfactory sensitivity was tested by an ascending staircase method using Butanol-1 or Vanilla extract. Results: A progressive tauopathy was found in the olfactory bulb and piriform cortex of transgenic human P301S tau mice. This was associated with progressive neuronal loss in the anterior and posterior piriform cortex. Furthermore, the human P301S tau mice displayed a significant reduction in olfactory sensitivity over time.Conclusions:We have observed progressive tau pathology, neuronal cell death and abnormal olfactory behavior in the human P301S tau transgenic mice. The olfactory alteration in this transgenic mouse line provides an in vivo system where to test mechanism-based therapies for the common and yet untreatable tauopathies.