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P3‐033: Vitamin D‐dependent regulation of gamma secretase complex
Author(s) -
Dursun Erdinc,
Atasoy Irem L.,
Alaylıoğlu Merve,
Yılmazer Selma,
Gezen-Ak Duygu
Publication year - 2015
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.2015.06.899
Subject(s) - calcitriol receptor , gene silencing , nicastrin , small interfering rna , microbiology and biotechnology , biology , neurotrophic factors , vitamin d and neurology , receptor , endocrinology , medicine , transfection , presenilin , biochemistry , gene , alzheimer's disease , disease
are unclear. Polyunsaturated fatty acids such as arachidonate (omega 6) and docosahexaenoic (omega 3) acids are highly abundant in the brain and are extremely vulnerable to oxidation due to their multiple double bonds. Indeed previously reported in vitro evidence suggests that amyloid beta proteins, in conjunction with transition metal ions, promote the oxidative degradation of polyunsaturated fatty acids into neurotoxic degradation products.Methods: Radiolabeled arachidonic acid was introduced via intracerebroventricular injection into mouse models of Alzheimer’s disease and the distribution and accumulation of degradation metabolites were monitored. In addition immunohistopathological analysis was performed with antibodies against HNE, an oxidized derivate of arachidonate, in human Alzheimer’s disease brains. Results: The oxidative degradation of arachidonate is markedly accelerated in regions of the brain where amyloid plaques are abundant. Studies of human Alzheimer’s disease brain show that amyloid plaques co-locate with proteins modified by hydroxynonenal. Conclusions: These results link several recurring themes in Alzheimer’s disease pathogenesis – amyloid beta protein accumulation, transition metal ions, oxidative stress, and altered fatty acid metabolism – into a single mechanism with the potential to account for neuronal loss in Alzheimer’s disease.