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Leptin is a peptide hormone secreted by adipose tissue. Studies have shown that leptin crosses the blood–brain barrier (BBB) by a saturable transport system where it acts within the hypothalamus to regulate food intake and energy expenditure. Leptin also acts in the hippocampus where it facilitates the induction of long-term potentiation and enhances NMDA receptor-mediated transmission. This suggests...
Amyloid β-peptide (Aβ) is the major constituent of senile plaques, a pathological hallmark of Alzheimer's disease (AD) brain. It is generally accepted that Aβ plays a central role in the pathophysiology of AD. Aβ is released from cells under entirely normal cellular conditions during the internalization and endosomal processing of amyloid precursor protein (APP). However, accumulation of Aβ can induce...
Dehydroepiandrosterone sulfate (DHEAS) has been reported to improve memory in aged animals and suggested as a treatment for age-related dementias. The SAMP8 mouse, a model of Alzheimer's disease, has an age-related impairment in learning and memory and an increase in brain levels of amyloid precursor protein (APP) and amyloid beta protein (Aβ). Male SAMP8 mice also have a decrease in testosterone,...
The blood-brain barrier (BBB) controls the exchange of peptides and regulatory proteins between the central nervous system (CNS) and the blood. Transport across the BBB of such regulatory substances is altered in animal models of Alzheimer's disease. These alterations could lead to cognitive impairments or diminish their therapeutic potential. Here, we measured the transport rate of radioactively...
There is now ample evidence that β-amyloid proteins decrease memory. The SAMP8 mouse (P8) develops an early decline in the ability to learn and to retain new information. The studies reviewed here suggest that this is due to overproduction of β-amyloid. Both antibodies to β-amyloid and specific antisense to the amyloid precursor protein reverse these deficits in the P8 mouse. This antisense can cross...
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