Deranged expression of molecular chaperones in brains of patients with Alzheimer's disease

Alzheimer's disease (AD) is one of the disorders caused by protein conforma tional changes and recent studies have shown that several chaperone protein s are involved in this process. As information of chaperone expression in A D brain is limited, we aimed to study the expressional pattern of chaperone s in several brain regions, as this may be essential to understand how fold ing defects can lead to disease. We studied the concomitant expressional pa tterns of molecular chaperones in seven brain regions of adults with AD usi ng two-dimensional polyacrylamide gel electrophoresis (2-DE) and matrix-ass ociated laser desorption ionization mass spectroscopy (MALDI-MS). We unambi guously identified and quantified nine different chaperone proteins. Sig ch aperone proteins, heat shock protein 60 (HSP 60), HSP 70 RY, heat shock cog nate (HSC) 71, alpha crystallin B chain, glucose regulated protein (GRP) 75 , and GRP 94 showed aberrant expressional patterns depending on brain regio n. HSP 70.1, GRP 78 and T-complex 1 (TCP-1) epsilon subunit did not show an y significant expressional change. These findings are compatible with neuro pathological and biochemical abnormalities in AD brain and this report pres ents the first approach to quantify nine different chaperones simultaneousl y at the protein level in individual AD brain regions providing evidence fo r the relevance of aberrant chaperone expression to AD neuropathology. (C) 2001 Academic Press.