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P2‐159: Identification of HPA axis dysfunction in ApoE targeted replacement mice
Author(s) -
Warwick Helen K.,
Jefferson Julius,
Zhou Hua,
Schack David,
Li Christine,
Ford Roger,
Li Zhuting,
Kirksey Yolanda,
Pangalos Menelas N.,
Reinhart Peter H.,
Riddell David R.
Publication year - 2009
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.2009.04.471
Subject(s) - endocrinology , medicine , apolipoprotein e , corticosterone , glucocorticoid , anterior pituitary , biology , hormone , adrenocorticotropic hormone , hippocampal formation , neurodegeneration , disease
brains and autopsy CSF samples by western blotting. Results: Analysis of 41 brain samples (25 AD, 72% apoE4 carriers; and 16 controls, 25% apoE4 carriers) showed that AD brains had significantly higher levels of apoE fragments than control brains. Western analysis of 92 human CSF samples (64 AD, 70% apoE4 carriers; 7 probable AD, 29% apoE4 carriers; and 21 controls, 14% apoE4 carriers) showed significantly higher levels of apoE fragments in AD patients with an apoE3/4 genotype than in controls with the same apoE genotype; no significant difference was detected between AD and control CSF samples with an apoE3/3 genotype. There was a trend toward higher fragment level, especially the smaller-sized fragments, in probable AD CSF samples as compared to controls. In AD brains, those with 1 and 2 apoE4 alleles showed a dose-response trend toward higher fragment level; the opposite trend was observed in AD CSF samples, suggesting that the apoE4 fragments might be preferentially retained in brains during the disease progression, as reported for Ab42. Conclusions: This preliminary study demonstrates that apoE fragmentation in AD brains and CSF samples is isoform and AD dependent and suggests that apoE fragment levels in CSF are a potential biomarker of AD with apoE4. Studies with more samples are needed to further evaluate the conclusion.