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[IC‐P‐047]: THE ROLE OF HIPPOCAMPAL SUBFIELDS IN THE ATROPHY PROCESS IN ALZHEIMER's DISEASE: AN IN‐VIVO STUDY OF THE ADNI COHORT
Author(s) -
Scelsi Marzia Antonella,
Iglesias Eugenio,
Schott Jonathan M.,
Ourselin Sebastien,
Altmann Andre
Publication year - 2017
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.2017.06.2319
Subject(s) - hippocampal formation , hippocampus , atrophy , cohort , biomarker , medicine , logistic regression , magnetic resonance imaging , neuroscience , alzheimer's disease , pathology , psychology , cardiology , nuclear medicine , disease , radiology , biology , biochemistry
amylin injures the brain microvessels independently of glucotoxicity, we infused aggregated human amylin (2 mg/g body weight, q.d., 7 days) into amylin gene knockout (AKO) rats. Results:Compared to WT rats, HIP rats showed gait abnormalities, impaired forelimb use, hind limb clasping, balance and learning. HIP rats had abnormalities in the white matter periventricular region including significantly enlarged ventricles (P1⁄40.002) and parenchymal loss (P1⁄40.003), compared toWT rats. Histological analysis of the white matter in HIP rats showed parenchymal rarefraction, significant loss of myelin basic protein (P<0.05) and luxol fast blue staining (P<0.05) in comparison toWT rats. Amylin deposition in brain microvessels of HIP rats was associated with disruption of vessel walls, capillary occlusion, and activated astrocytes. HIP rats also have significantly increased brain microhemorrhages (P1⁄40.04). Lower retrieved fluorescent microspheres in HIP brain capillaries than in WT (P1⁄40.01) suggests brain hypoperfusion. AKO rats infused with aggregated amylin showed brain microhemorrhages and vascular astrocyte recruitment; however, the white matter appeared intact by in vivoMRI. The results suggest that white matter injury is downstream of amylin-mediated vascular injury. Conclusions:Systemic amylin dyshomeostasis is a mediator of microvascular injury to the brain that can cause white matter disease and behavior changes.