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Alzheimer’s‐like behavior and pathology in a transgenic mouse model of Down syndrome (651.9)
Author(s) -
Noterman Maria,
Deyo Richard,
Mann Francis
Publication year - 2014
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.28.1_supplement.651.9
Subject(s) - down syndrome , neuropathology , chromosome 21 , trisomy , hippocampal formation , hippocampus , alzheimer's disease , pathology , neuroscience , genetically modified mouse , biology , psychology , medicine , disease , transgene , chromosome , genetics , gene
Down syndrome (DS) is caused by trisomy of human chromosome 21 (Hsa21) and is correlated with various comorbidities, including Alzheimer’s disease in 50% of affected individuals. The Tc1 mouse model contains a copy of Hsa21, producing an animal model of DS. In an effort to understand the correlation between DS and Alzheimer’s disease, this study evaluated the learning, memory, and hippocampal and cortical brain morphology in the Tc1 mouse model. Genotyping of Tc1 mice indicated that Hsa21 was transmitted with a 16.67% frequency. Tc1 mice underwent open field, dark‐light, and step down test of inhibitory avoidance tests at set timepoints. Increased hypomotor and anxiety‐related activity in was identified in Hsa21 positive animals. Acquisition of hippocampal‐dependent short‐term memory was intact while long‐term memory trended towards impairment. Relative brain weight of Hsa21 positive subjects was significantly higher than control littermates with lateral ventricle area profoundly increased. Histological screening for Alzheimer’s‐like neuropathology showed neurofibrillary tangles in the cortex of all Hsa21+ mice and a diffuse plaque in one Hsa21+ subject. Immunohistochemistry was used to analyze beta‐amyloid 1‐42 levels in control and Hsa21+ mice. This heterogeneity in pathology is consistent with the spectrum of neuropathological deficits, including Alzheimer’s, seen in patients with DS.