A peptidyl-prolyl isomerase, FKBP12, accumulates in Alzheimer neurofibrillary tangles.
We investigated a possible role in Alzheimer's disease (AD) for FKBP12, a peptidyl-prolyl cis-trans isomerase known to be important in protein assembly, folding and transportation by using Western blotting and microscopic analyses in postmortem brain tissues from elderly controls and the patients with AD. FKBP12 was enriched and localized to neuronal cell bodies and neurites in control brains. Intense immunoreactivity was found in large neurons such as pyramidal cells. Many FKBP12 positive granules were located in the cytoplasm and the proximal portion of dendrites and axons, and in the nuclei. By contrast, the expression of FKBP12 in AD brains was lower than in control brains. Furthermore, numerous intracellular neurofibrillary tangles (NFTs) were stained for FKBP12 in the hippocampal CA1 subfield, subiculum, entorhinal cortex and angular gyrus. Neuritic pathology such as neuropil threads and dystrophic neurites (DNs) within senile plaques (SPs) and some reactive astrocytes were also immunolabeled for FKBP12 in AD. Double immunofluorescence staining showed dual labeling of intracellular NFTs for FKBP12 and tau. Similar results were obtained in reactive astrocytes for the combination of FKBP12 and glial fibrillary acidic protein (GFAP). Labeling for FKBP12 was dense in axons stained for highly phosphorylated neurofilament protein. Thus our results suggest that FKBP12 may be involved in neuronal or astrocytic cytoskeletal organization and in the abnormal metabolism of tau protein in AD damaged neurons.
Department of Rehabilitation Science, Kobe University Graduate School of Health Sciences, 7-10-2 Tomogaoka, Suma-ku, Kobe, Japan.
Hisato
H
Sugata
Kazuhiko
K
Matsuo
Taisuke
T
Nakagawa
Mikiko
M
Takahashi
Hideyuki
H
Mukai
Yoshitaka
Y
Ono
Kiyoshi
K
Maeda
Haruhiko
H
Akiyama
Toshio
T
Kawamata
D000368:Aged; D000369:Aged, 80 and over; D000544:Alzheimer Disease / Q000201:enzymology* / Q000378:metabolism; D001253:Astrocytes / Q000201:enzymology / Q000378:metabolism; D001369:Axons / Q000201:enzymology / Q000378:metabolism; D001921:Brain / Q000201:enzymology* / Q000378:metabolism; D005260:Female; D005904:Glial Fibrillary Acidic Protein / Q000378:metabolism; D006801:Humans; D008297:Male; D008875:Middle Aged; D016874:Neurofibrillary Tangles / Q000201:enzymology* / Q000378:metabolism; D016900:Neurofilament Proteins / Q000378:metabolism; D009474:Neurons / Q000201:enzymology* / Q000378:metabolism; D010766:Phosphorylation; D058225:Plaque, Amyloid / Q000201:enzymology; D022061:Tacrolimus Binding Protein 1A / Q000378:metabolism*; D016875:tau Proteins / Q000378:metabolism
D005904:Glial Fibrillary Acidic Protein; C054369:MAPT protein, human; D016900:Neurofilament Proteins; D016875:tau Proteins; D022061:Tacrolimus Binding Protein 1A