BACKGROUND: @entity195 ( @entity195 ) is a @entity179 characterized by amyloid-b (Ab) plaque formation, tau pathology, @entity179 and inflammatory processes. Monocytes are involved in @entity32 in @entity195 and are recruited to the diseased brain. Recently it has been shown that aberrant epigenetic processes including acetylation are associated with the development of @entity195 . The aim of the present study was to examine acetylation of histone H4 at @entity376 12 (H4K12) in monocytes in two transgenic @entity195 @entity19 models (the triple transgenic 3xTg and a model overexpressing amyloid-precursor protein APP with the Swedish-Dutch-Iowa mutations), and to compare with monocytes isolated from @entity1 @entity1 with @entity73 ( @entity73 ) and @entity195 . METHODS: @entity19 and @entity1 monocytes were selectively isolated with a positive (PluriSelect) respectively with a negative selection method (Miltenyi). Histones were extracted and acetylation of H4K12 was analyzed by a quantification fluorometric kit. Moreover, monocyte cytokine release was measured and cell death analyzed by FACS using incorporation of 7-AAD. RESULTS: Our data show a significant increase of monocytic H4K12 acetylation in both transgenic @entity195 @entity19 models early during development of the plaque deposition in the brain. In line with these data we found significantly elevated acetylation of H4K12 in @entity1 @entity1 with @entity73 but not in @entity1 with @entity195 . Along with these observations we found that the monocytes of @entity195 @entity19 and of @entity195 @entity1 were significantly more vulnerable to cell damage (as seen by 7-AAD incorporation in FACS analysis) and displayed an enhanced release of pro-inflammatory cytokines ( @entity10149 and @entity310 ). CONCLUSION: Our findings indicate that epigenetic changes in peripheral monocytes are an early event in @entity195 -pathology. Thus H4K12 acetylation may be considered as a novel biomarker for early changes in @entity195 development.

Increased acetylation of histone H4 at @entity376 12 (H4K12) in monocytes of transgenic Alzheimer's XXXX and in @entity1 @entity1 .

@entity1 :: ('9606', 'Species') :: ['human', 'patients'] @entity32 :: ('MESH:D007249', 'Disease') :: ['inflammation'] @entity19 :: ('10090', 'Species') :: ['mice', 'Mouse', 'mouse'] @entity73 :: ('MESH:D003072', 'Disease') :: ['MCI', 'mild cognitive impairment'] @entity310 :: ('7124', 'Gene') :: ['TNFa'] @entity376 :: ('CHEBI:25094', 'Chemical') :: ['lysine'] @entity179 :: ('MESH:D019636', 'Disease') :: ['neurodegeneration', 'neurodegenerative disorder'] @entity10149 :: ('2920', 'Gene') :: ['MIP2'] @entity195 :: ('MESH:D000544', 'Disease') :: ['AD', "Alzheimer's disease"]
@entity19 :: (10090,Species) :: ['mice']
