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P4‐191: Gwas identifies gli3 as a novel gene for language deficits and cortical changes in older adults at‐risk for Alzheimer's disease
Author(s) -
Deters Kacie,
Nho Kwangsik,
Risacher Shan L.,
Kim Sungeun,
Ramanan Vijay K.,
Crane Paul K.,
Saykin Andrew J.
Publication year - 2015
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.2015.08.019
Subject(s) - genome wide association study , psychology , alzheimer's disease neuroimaging initiative , verbal fluency test , audiology , neuropsychology , single nucleotide polymorphism , neuroscience , medicine , cognition , biology , genetics , cognitive impairment , genotype , gene
than mice with APP or tau expression (Figure). The cognitive deficits developed well before the first plaques or pre-tangles and coincided with changes in parvalbumin-positive (PV) interneurons and PV plexus in the dentate gyrus (DG) of the hippocampus. Disruption of this inhibitory circuit was followed by progressive and selective neurodegeneration of DG, a phenomena that was not observed in mice expressing single APP or tau. Conclusions:Data on MAO tTa:APPsi model indicate that starting as early as middle age, sensitivity to toxic effects of Ab appears to increase. Using the same MAO approach, we show that co-expression of APP and tau augments cognitive deficits and results in neurodegeneration of DG. PV interneurons of DG did not produce APP or tau, however appeared to have high vulnerability to the effects of APP and tau initiating the cascade that culminated in neurodegeneration of dentate granule cells.