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P2‐424: EARLY DETECTION OF BRAIN HYPOMETABOLISM IN THE 3XTG MOUSE MODEL OF ALZHEIMER'S DISEASE
Author(s) -
Adlimoghaddam Aida,
Goertzen Andrew,
Ko Ji Hyun,
Snow Wanda M.,
Stortz Greg,
Djordjevic Jelena,
Perez Claudia,
Albensi Benedict C.
Publication year - 2018
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.2018.06.1116
Subject(s) - neuropathology , pathology , alzheimer's disease , cytochrome c oxidase , pathological , dementia , medicine , amyloid (mycology) , neuroscience , mitochondrion , disease , biology , biochemistry
over time. Methods:We used dMRI data from healthy elderly subjects from the Alzheimer’s Disease Neuroimaging Initiative (ADNI: 23/73 APOE4 carriers/non-carriers; 2-4 time-points) and Singapore Longitudinal Ageing Brain Study (S-LABS: 21/73 APOE4 carriers/non-carriers; 2-3 time-points). We derived subject-specific FW and FAt maps from dMRI data and averaged over the whole-brain WM and 18 major WM fibres traced using the TRACULAmethod (Yendiki et al., 2016). Linear mixed models assessed the contribution of cross-sectional age, time and APOE genotype (E4 carrier/non-carrier) on FW and FAt longitudinal trajectories. Covariates included gender, years of education and estimated total intracranial volume. Results: APOE4 carriers exhibited larger increases in average FW over time than non-carriers in ADNI (APOE4*age*time; p<0.05) and S-LABS (APOE4*time; p<0.05; Fig.1). Specifically, APOE4 carriers had greater FW increases in the right cingulum angular bundle (CAB) for S-LABS (p1⁄40.003; Fig.2) and bilateral CAB for ADNI (p<0.05). APOE4 carriers that were older at baseline showed steeper reduction in left CAB FAt over time in S-LABS (APOE4*age*time; p<0.05; Fig.3). Moreover, APOE4 carriers had faster FAt decline (S-LABS) and greater age-dependent FW increases (ADNI) in the right inferior longitudinal fasciculus (p<0.05; Fig.4). Conclusions:Across the two datasets, we consistently demonstrated that the presence of APOE4 allele in healthy elderly appears to be associated with greater neuroinflammation, mild vascular changes and excessive WM degeneration over time in temporal-parietal and temporal-occipital fibres.