Abstract
Alzheimer’s disease (AD) is the most common neurodegenerative dementia. Mapping the pathomechanism and providing novel therapeutic options have paramount significance. Recent studies have proposed the role of LMTK2 in AD. However, its expression pattern and association with the pathognomonic neurofibrillary tangles (NFTs) in different brain regions and neuropathological stages of AD is not clear. We performed chromogenic (CHR) LMTK2 and fluorescent phospho-tau/LMTK2 double-labelling (FDL) immunohistochemistry (IHC) on 10–10 postmortem middle frontal gyrus (MFG) and anterior hippocampus (aHPC) samples with early and late neuropathological Braak tau stages of AD. MFG in early stage was our ‘endogenous control’ region as it is not affected by NFTs. Semiquantitative CHR-IHC intensity scoring revealed significantly higher (p < 0.001) LMTK2 values in this group compared to NFT-affected regions. FDL-IHC demonstrated LMTK2 predominance in the endogenous control region, while phospho-tau overburden and decreased LMTK2 immunolabelling were detected in NFT-affected groups (aHPC in early and both regions in late stage). Spearman’s correlation coefficient showed strong negative correlation between phospho-tau/LMTK2 signals within each group. According to our results, LMTK2 expression is inversely proportionate to the extent of NFT pathology, and decreased LMTK2 level is not a general feature in AD brain, rather it is characteristic of the NFT-affected regions.
Highlights
Alzheimer’s disease (AD) is the most common cause of dementia, affecting more than 47 million people worldwide [1]
neurofibrillary tangles (NFTs) burden inversely correlates with the number of surviving neurons, proposing that neurofibrillary lesions have a key role in degenerative changes and apoptotic cell loss in AD [10]
The latest studies suggest that there is a link between the expression/activity of recently described lemur tyrosine kinase 2 (LMTK2) protein and tau hyperphosphorylation [11,12,13]
Summary
Alzheimer’s disease (AD) is the most common cause of dementia, affecting more than 47 million people worldwide [1]. It was first described by Alois Alzheimer in 1906 [2]. The main constituent of NFTs is the microtubule-associated protein tau. Braak and Braak first described the hierarchy of NFT spreading in the central nervous system [9]. They established six stages based on the affected brain regions: transentorhinal stages (I-II); limbic stages (III-IV); and isocortical stages (V-VI). The latest studies suggest that there is a link between the expression/activity of recently described lemur tyrosine kinase 2
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