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P1‐116: Classifying TAU Pet Positivity with [18F]‐AV‐1451 in Preclinical Alzheimer's Disease
Author(s) -
Mishra Shruti,
Gordon Brian Andrew,
Friedrichsen Karl A.,
Su Yi,
Christensen Jon,
Aldea Patricia,
Cairns Nigel J.,
Morris John C.,
Ances Beau,
Benzinger Tammie LS.
Publication year - 2016
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.2016.06.864
Subject(s) - entorhinal cortex , clinical dementia rating , standardized uptake value , psychology , tau pathology , nuclear medicine , dementia , temporal cortex , neuroscience , hippocampus , alzheimer's disease , medicine , pathology , positron emission tomography , cognitive impairment , disease , cognition
Background: Intracerebral inoculation of brain homogenates containing misfolded amyloid beta (Abeta) proteins leads to nucleation and propagation processes accelerating amyloid deposition in transgenic mice. Factors modulating nucleation and propagation processes are still partly unknown. Local environment seems to be critical and several studies suggest that regional differences in Abeta deposition following AD-brain inoculation closely resemble the normal age-related deposition of Abeta in the brain. For example, few deposits were reported after inoculation in the striatum. Many possible ways of propagation have been reported: passive diffusion in the extracellular space, propagation through the connectome, diffusion through basement membrane of the vessels. Here we characterized Abeta nucleation and propagation processes in APPSwe/PS1DeE9 mice. Methods: We performed bilateral stereotaxic inoculation of brain homogenates from two AD patients (Braak stage VI and Thal stages 5 and 4, respectively) and one control agematched subject in the hippocampus of 8 week-old APPSwe/ PS1DeE9 mice (n1⁄440). Post-mortem evaluation at one, two and four months post-inoculation was performed using immunohistochemistry (BAM10 antibody). Results: Amyloid deposition following AD homogenates inoculation occurred mainly within the corpus callosum (CC) and not in other brain regions usually involved with age-related amyloid deposition such as the hippocampus and the cortex. We showed that intrahippocampal inoculation of AD homogenates induces a progressive and stereotyped callosal amyloidosis which differs from the normal age-related deposition of Abeta. Conclusions: Intra-hippocampal inoculation of human AD brain homogenates led to striking acceleration of amyloidosis in the CC subjacent to the hippocampus in APPSwe/PS1DeE9. APPSwe, expressed under prion promoter, is poorly expressed in the CC. Soluble amyloid could migrate from its production areas towards CC and be trapped within early amyloiddeposits occurring in theCCafter inoculation to increase the amyloid load over time. Regarding the diffusion of amyloid, our study suggests that white matter tracts have to be considered as a possible pathway leading to the propagation of amyloidosis in transgenicmice.References:1. Meyer-Luehmann, Science, 2006; 2. Eisele, PNAS, 2009; 3. Duyckaerts, Acta Neuropathol., 1997; 4. Ye, Brain Pathol., 2015; 5. Thal, Front AgingNeurosci., 2015; 6.Maskri, Neurodegen. Dis., 2004. Jankowsky, Biomolecular Engineer, 2001. Work supported by the France-Alzheimer Association and by the Foundation Plan Alzheimer.