Alzheimer's Disease Research Today is a free monthly online journal that collates and summarizes the latest research about Alzheimer's Disease, including details on diagnosis, memory loss, heredity, treatment, medication.

Identification of a mutant-like conformation of p53 in fibroblasts from sporadic Alzheimer's disease patients.

Uberti D, Lanni C, Carsana T, Francisconi S, Missale C, Racchi M, Govoni S, Memo M

Department of Biomedical Sciences and Biotechnologies, University of Brescia, Viale Europa 11, 25124 Brescia, Italy. uberti@med.unibs.it

Here we show that fibroblasts from sporadic Alzheimer's disease (AD) patients specifically express an anomalous and detectable conformational state of p53 that makes these cells distinct from fibroblasts of age-matched non-AD subjects. In particular, we found that, in contrast to non-AD fibroblasts, p53 in AD fibroblasts is expressed at higher levels in resting condition, and presents a significant impairment of its DNA binding and transcriptional activity. All together, these findings figured out the presence of a mutant-like p53 phenotype. However, gene sequencing of the entire p53 gene from either AD or non-AD did not unravel point mutations. Based on immunoprecipitation studies with conformation-specific p53 antibodies (PAb1620 and PAb240), which discriminated folded versus unfolded p53 tertiary structure, we found that a significant amount of p53 assumed an unfolded tertiary structure in fibroblasts from AD patients. This conformational mutant-like p53 form was virtually undetectable in fibroblasts from non-AD patients. These data, independently from their relevance in understanding the etiopathogenesis of AD, might be useful for supporting AD diagnosis.

Published 24 July 2006 in Neurobiol Aging, 27(9): 1193-201.
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