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[P3–153]: THE INFLUENCE OF AMYLOID‐B PRECURSOR PROTEIN PROTEOLYTIC PROCESSING ON NEURONAL IRON HOMEOSTASIS
Author(s) -
Wong Bruce X.,
Tsatsanis Andrew,
Lam Linh Q.,
Ayton Scott,
Gunn Adam P.,
Devos David,
Bush Ashley I.,
Duce James A.
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.2017.06.1365
Subject(s) - amyloid precursor protein , neurotoxicity , ferroportin , chemistry , intracellular , microbiology and biotechnology , reactive oxygen species , alpha secretase , biochemistry , biology , alzheimer's disease , iron homeostasis , toxicity , medicine , metabolism , disease , organic chemistry
Background: Reduced plasma 25-hydroxyvitamin D (25-OH-D) was proved to be associated with poorer cognitive function and a higher risk of developingAlzheimer’s disease (AD), but the specific mechanisms were unknown. Increased vascular injury due to activation of renin-angiotensin-system is one of the hypotheses about the relationship between vitamin D and AD.Methods:We recruited patients with early AD from two teaching hospitals in Taiwan. All patients underwent clinically functional assessment and a neuropsychological test battery. Plasma 25-OH-D level was checked by radioimmunoassay. Brain magnetic resonance imaging (MRI) was used to determine the volume of white matter hyperintensities (WMH), a surrogate of cerebral vascular injury. We analyzed the relationship between cognitive function, plasma level of 25-OHD, and WMH volume in early AD patients. Results: In total, 146 early AD patients (68 males/78 females; mean age 79.1 6 7.0 years; mean education 10.2 6 4.3 years) were recruited. Their mean Mini-Mental State Examination (MMSE) was 21.0 6 3.8. The clinical dementia rating (CDR) score was 0.5 in 24 patients and 1.0 in 123 patients. The percentage of APOE ε4 carrier was 35.4 %. The correlation analysis between WMH volume and 25OH-D level showed significant negative correlation (R 1⁄4 0.086, adjusted p 1⁄4 0.003, adjusting age, sex, hypertension, diabetes mellitus, hyperlipidemia, and coronary heart disease). The correlation analysis between MMSE and 25-OH-D level showed significant positive correlation (R 1⁄4 0.067, adjusted p 1⁄4 0.002, adjusting age, sex, and education years). Multivariate regression analysis, performed by using MMSE as the dependent variable and adjusting age, sex, and education years, showed 25-OH-D level was an independent predictor for MMSE score (b 1⁄4 0.25, p 1⁄4 0.003), but WMH volume was not (b1⁄4 -0.02, p1⁄4 0.82). Conclusions:Reduced plasma 25-OH-D was associated with low MMSE scores in early AD patients. The underlying mechanisms were partially attributed to cerebral vascular injury, and it also suggested the presence of other different mechanisms.