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IC–P–055: fMRI studies of hippocampal dysfunction and therapeutic response in mouse models of Alzheimer's disease
Author(s) -
Moreno Herman,
Lee Thomas,
Yu Rui,
Small Scott A.
Publication year - 2006
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.2006.05.2260
Subject(s) - hippocampal formation , entorhinal cortex , neuroscience , hippocampus , medicine , psychology
very early stage DAT). Methods: We recently investigated the relationship between the in vivo amyloid load (via PET imaging of the amyloid-binding compound, C-PIB) and various CSF measures in a small (n 24) research cohort (age 48-83 years) that included both cognitively normal individuals and those diagnosed with very mild or mild DAT (Fagan et al., 2006, Ann. Neurol.). Results: We observed a striking inverse relation between mean cortical amyloid load and CSF A 42 (but not other CSF markers); those with positive PIB-binding had low CSF A 42 levels and those with negative PIB-binding had high CSF A 42 levels, with no overlap between the two groups. Importantly, this pattern was observed in a subset of subjects who were cognitively normal, suggesting the presence of amyloid pathology in the absence of cognitive symptoms (“preclinical AD”). These findings suggest that brain amyloid deposition results in low CSF A 42, and that amyloid imaging and CSF A 42 may potentially be useful as antecedent biomarkers of (preclinical) AD. We have since expanded our cohort size and will provide an update of our findings, including the consistency of this pattern in this larger sample, the degree to which it is maintained in individuals exhibiting a relatively low level of brain amyloid, and whether analyses of regional PIB binding offer additional discriminatory power. Conclusions: These additional analyses will provide important information regarding the potential utility of these measures as diagnostic and/or antecedent biomarkers of AD and may also offer insights into possible mechanism(s) of amyloid deposition in the AD brain.