24 January 2002. More women than men have Alzheimer's disease (AD), suggesting
that loss of estrogen may increase the risk for AD in postmenopausal women.
Recent studies to demonstrate that estrogen protects Alzheimer's patients have
had mixed results. In the January 22 advanced online publication in PNAS, Sozos
Papasozomenos and Alikunju Shanavas at the University of Texas demonstrate that
testosterone may prove beneficial in preventing the disease.
The researchers used an animal model to test the effects of testosterone and
estradiol on heat shock induced phosphorylation of tau, the major component
of the neurofibrillary tangles that are associated with AD. They found that
testosterone, but not estradiol, could prevent phosphorylation of the microtubule-associated
protein, specifically at Ser404.
Extracts from the forebrains of heat-shocked rats were tested for activity
of glycogen synthase kinase-3β GSK-3β
, cyclin-dependent kinase 5 (Cdk5), and c-Jun N-terminal kinase (JNK), which
had previously been shown to be involved in tau phosphorylation. In the presence
of testosterone, only GSK-3β activity was affected,
being significantly reduced. Using phosphospecific antibodies, the authors showed
the androgen to prevent phosphorylation of Tyr216, which is required for full
activation of the kinase.
This work provides a molecular basis for previous observations that men with
lower plasma testosterone are more susceptible to developing Alzheimer's.-Tom Fagan.
Papasozomenos SCh, Shanavas A. Testosterone prevents
the heat shock-induced overactivation of glycogen synthase kinase-3β
but not of cyclin-dependent kinase 5 and c-Jun NH2-terminal kinase
and concomitantly abolishes hyperphosphorylation of t:
Implications for Alzheimer's disease. PNAS advance online publication 22 January
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