Alzheimers disease (Advertisement) is the most common neurodegenerative dementia. between phospho-tau/LMTK2 signals within each group. According to our results, LMTK2 manifestation is definitely inversely proportionate to the degree of NFT pathology, and decreased LMTK2 level is not a general feature in AD mind, rather it is characteristic of the NFT-affected areas. = 10 in total) with early (Braak stage III or less, = 5) and late stage (Braak stage VI, = 5) pathological changes (Table 1). The majority of the individuals in the early neuropathological stage group experienced slight dementia. In the late neuropathological stage group, every patient suffered from severe dementia. Participants were included at time of analysis of dementia and adopted annually until loss of life. Dementia was diagnosed according to DSM IV criteria, and AD was diagnosed according to the National Institute of Neurological and Communicative Disorders and Association. Mild dementia was defined as mini-mental state examination (MMSE) score 20 and/or Clinical Dementia Rating score = 1. The clinical evaluation included standardized scales, and cognition was measured using MMSE and a neuropsychological test battery. In addition, blood tests and MRI scans were performed to rule out other causes for cognitive decline. More details of the study design are provided in our previous work [20]. Block taking for histological and immunohistochemical studies and neuropathological assessment for neurodegenerative diseases was carried out in accordance with standard criteria as described in detail in earlier studies [21]. Table 1 Human postmortem samples: case identifier (study ID), age (baseline), sex, final MMSE score, Hoxa10 neuropathological Braak tau stage and APOE gene polymorphism. (M: male; F: female; MMSE: mini-mental state examination; APOE: apolipoprotein E). < 0.001 (***)) differences between pairwise comparison of the mean intensity scores of early neuropathological stage MFG group (endogenous controlspared from neurofibrillary tangles (NFTs)) vs. NFT-affected groups (aHPC in early neuropathological stage and both regions BMS-345541 in late neuropathological stage). Table 2 Statistical analysis of lemur tyrosine kinase 2 (LMTK2) (red)/phospho-tau (green) fluorescent signal correlation in the middle frontal gyrus (MFG) and anterior hippocampus (aHPC) in early and late neuropathological Braak tau stages < 0.001) in BMS-345541 the mean LMTK2 immunolabelling intensity scores compared to the relatively spared middle frontal gyrus in early neuropathological stage (Figure 2). Among the LMTK2 intensity scores of the three NFT-affected regions there were no statistically significant differences. According to ANCOVA, neither age (= 0.137) nor final MMSE score (= 0.132) nor APOE gene polymorphism (= 0.253) significantly influenced the LMTK2 CHR-IHC results. 3.2. Fluorescent Double-Labelling Immunohistochemistry (FDL-IHC) Phospho-tau/LMTK2 FDL-IHC showed LMTK2 predominance in the endogenous control group (MFG in early neuropathological stage), while phospho-tau overburden and decreased LMTK2 immunolabelling were detected in NFT-affected groups (aHPC in BMS-345541 early and both regions in late neuropathological stage) (Figure 3). The measured percentage distribution of phospho-tau/LMTK2 values of the individual cases are visualized in Figure 4. Group level comparison of LMTK2 (red) and phospho-tau (green) fluorescent signals, derived from the case-based evaluation, are shown in Figure 5. Open in a separate window Figure 3 Lemur tyrosine kinase 2 (LMTK2) and phospho-tau fluorescent double-labelling immunohistochemistry in the middle frontal gyrus (MFG) in early (ACC) and late (DCF) neuropathological Braak tau stages. LMTK2 immunolabelling (red) dominates the early neuropathological stage (A,C), which is spared by neurofibrillary tangles (NFT), while there is an obvious phospho-tau burden (E,F) with decreased LMTK2 positivity (D) in the late neuropathological stage. LMTK2 and phospho-tau were visualized by Alexa Fluor 594 and Alexa Fluor 488 fluorescent dyes, respectively..