PTEN levels in Alzheimer's disease medial temporal cortex.
Phosphatase and tensin homologue deleted from chromosome 10 (PTEN) is a dual (protein tyrosine and lipid) phosphatase one of the functions of which is to dephosphorylate phosphatidylinositol 3,4,5-trisphosphate to phosphatidylinositol-3,4-biphosphate thereby inhibiting phosphoinositide-dependent kinase activation of the cell survival kinase Akt. Akt activity is up regulated in Alzheimer's disease (AD) brain in parallel to the progression of neurofibrillary pathology. The present study determined whether altered expression of PTEN occurs in Alzheimer's disease brain. Western immunoblotting revealed no significant changes of PTEN protein levels in nuclear and membrane fractions of medial temporal cortex from a series of Alzheimer's disease and control cases. Similarly, no changes in PTEN protein levels, as determined by dot-blotting, were seen in temporal cortex homogenates from a separate series of Alzheimer's disease and control brains. A small but significant decrease in the levels of Ser(380) p-PTEN was seen in homogenates of Alzheimer's disease temporal cortex. Immunohistochemistry revealed PTEN immunoreactivity in a number of brain structures including neurons, capillaries and structures resembling oligodendrocytes and astrocytes. The majority of temporal cortex pyramidal neurons (93-100%) were PTEN immunopositive. The Alzheimer's disease cases had significantly lower numbers of total ( approximately 12% loss, P<0.02) and PTEN immunopositive ( approximately 15% loss, P<0.01) pyramidal neurons as compared to the control cases.
Rickle
Annika
A
Karolinska Institutet Sumitomo Pharmaceuticals Alzheimer Center (KASPAC), Department of Neurotec, Division of Experimental Geriatrics, Neurotec, Novum Plan 5, S141 57 Huddinge, Sweden.
Bogdanovic
Nenad
N
Volkmann
Inga
I
Zhou
Xinwen
X
Pei
Jin-Jing
JJ
Winblad
Bengt
B
Cowburn
Richard F
RF
D000368:Aged; D000369:Aged, 80 and over; D000544:Alzheimer Disease / Q000378:metabolism*; D015153:Blotting, Western; D016022:Case-Control Studies; D005260:Female; D006801:Humans; D007150:Immunohistochemistry; D008297:Male; D051059:PTEN Phosphohydrolase / Q000378:metabolism*; D013702:Temporal Lobe / Q000378:metabolism*
D051059:PTEN Phosphohydrolase; C494929:PTEN protein, human