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2014 ; 6
(2
): 17
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TMEM106B expression is reduced in Alzheimer s disease brains
#MMPMID24684749
Satoh J
; Kino Y
; Kawana N
; Yamamoto Y
; Ishida T
; Saito Y
; Arima K
Alzheimers Res Ther
2014[]; 6
(2
): 17
PMID24684749
show ga
INTRODUCTION: TMEM106B is a transmembrane glycoprotein of unknown function
located within endosome/lysosome compartments expressed ubiquitously in various
cell types. Previously, the genome-wide association study (GWAS) identified a
significant association of TMEM106B single nucleotide polymorphisms (SNPs) with
development of frontotemporal lobar degeneration with ubiquitinated TAR
DNA-binding protein-43 (TDP-43)-positive inclusions (FTLD-TDP), particularly in
the patients exhibiting the progranulin (PGRN) gene (GRN) mutations. Recent
studies indicate that TMEM106B plays a pathological role in various
neurodegenerative diseases, including Alzheimer's disease (AD). However, at
present, the precise levels of TMEM106B expression in AD brains remain unknown.
METHODS: By quantitative reverse transcription (RT)-PCR (qPCR), western blot and
immunohistochemistry, we studied TMEM106B and PGRN expression levels in a series
of AD and control brains, including amyotrophic lateral sclerosis, Parkinson's
disease, multiple system atrophy and non-neurological cases. RESULTS: In AD
brains, TMEM106B mRNA and protein levels were significantly reduced, whereas PGRN
mRNA levels were elevated, compared with the levels in non-AD brains. In all
brains, TMEM106B was expressed in the majority of cortical neurons, hippocampal
neurons, and some populations of oligodendrocytes, reactive astrocytes and
microglia with the location in the cytoplasm. In AD brains, surviving neurons
expressed intense TMEM106B immunoreactivity, while senile plaques,
neurofibrillary tangles and the perivascular neuropil, almost devoid of TMEM106B,
intensely expressed PGRN. CONCLUSIONS: We found an inverse relationship between
TMEM106B (downregulation) and PGRN (upregulation) expression levels in AD brains,
suggesting a key role of TMEM106B in the pathological processes of AD.