The epigenetic remodeling of chromatin histone proteins by acetylation has been 
the subject of recent investigations searching for biomarkers indicative of late 
onset cognitive loss. Histone acetylations affect the regulation of gene 
transcription, and the loss of learning induced deacetylation at specific 
histone sites may represent biomarkers for memory loss and Alzheimer's disease 
(AD). Selected-reaction-monitoring (SRM) has recently been advanced to 
quantitate peptides and proteins in complex biological systems. In this paper, 
we provide evidence that SRM-based targeted proteomics can reliably quantify 
specific histone acetylations in both AD and control brain by identifying the 
patterns of H3 K18/K23 acetylations Results of targeted proteomics assays have 
been validated by Western blot (WB) analysis. As compared with LC-MS/MS-TMT 
(tandem-mass-tagging) and WB methods, the targeted proteomics method has shown 
higher throughput, and therefore promised to be more suitable for clinical 
applications. With this methodology, we find that histone acetylation is 
significantly lower in AD temporal lobe than found in aged controls. Targeted 
proteomics warrants increased application for studying epigenetics of 
neurodegenerative diseases.