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P1‐376: A‐beta 42 and A‐beta 40 fibrillation, in vitro, is affected to different extents by environmental stress factors
Author(s) -
Ahmad Atta
Publication year - 2010
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.2010.05.930
Subject(s) - kinetics , in vitro , amyloid (mycology) , amyloid beta , disease , fibrillation , chemistry , calcium , biophysics , biochemistry , medicine , neuroscience , biology , atrial fibrillation , pathology , physics , quantum mechanics
sporadic in origin. The cause of sporadic AD is likely to be multifactorial, with external factors interacting with biological or genetic susceptibilities to accelerate the manifestation of the disease. Diabetes mellitus (DM) might be such factor, as there is extensive data from epidemiological studies suggesting that DM is associated with an increased relative risk for Alzheimer’s disease. Type 1 diabetes (T1DM) and type 2 diabetes (T2DM) are known to affect multiple cognitive functions in patients. However, the consequences of both type of diabetes on tau pathology are not well understood. Methods: We wanted to investigate whether T1DM and T2DM induce tau pathology in different models of diabetes. For T1DM, we used a genetic model (Non Obese Diabetic), or we induced it with streptozotocin. For T2DM we used a genetic model (db/db mice), or we induced it with high fat diet. For all these models we investigated tau pathology and its mechanism. Results: We observed tau hyperphosphorylation in all the forms of diabetes. However, the mechanism of tau phosphorylation was different between T1DM and T2DM. Conclusions: Our data indicate that: i) diabetes induced abnormal tau hyperphosphorylation in the brain of normal mice, with biochemical, regional and histochemical patterns resembling those in early AD brains. ii) diabetes induced tau hyperphosphorylation through two distinct mechanisms between T1DM and T2DM. This research will help the development of treatments or life-style strategies destined to check the advance of the disease.