Potential Predictive Test Found For Alzheimer's Disease

A protein has been described that may prevent hyperphosphorylation of Tau protein, in diseases like Alzheimer's disease (AD) and can be used as a predictive diagnostic tool.

The fujimycin binding protein 52 (FKBP52) is a member of the immunophilin protein family, which play a role in immunoregulation and basic cellular processes involving protein folding and trafficking, and has been shown to characterize a number of cerebral neurodegenerative diseases.

Scientists at the Institut National de la Santé et de la Recherche Médicale (INSERM; Paris, France) demonstrates a direct correlation between high levels of hyperphosphorylated Tau protein and reduced levels of FKBP52, in brain cells from patients who have died following Alzheimer's Disease, compared with normal brain cells. This suggests that FKBP52 could control the aberrant production of pathogenic Tau. When FKBP52 is reduced in the nerve cells of AD patients, pathogenic Tau is free to accumulate and contribute to the degeneration of brain cells.

The investigators analyzed the expression of FKBP52 in human brains of patients with different tauopathies, including AD. Immunohistofluorescence studies carried out on cerebral cortex in different tauopathies reveal that FKBP52 is not sequestered by filamentous tau inclusions while FKBP52 is co-localized with tau in the control case brains. They found that FKBP52 expression level is abnormally low in frontal cortex of AD and microtubule-associated protein tau (FTDP-17) brains, as compared to controls, despite no alteration in the FKBP52 messenger ribonucleic acid (mRNA) expression level.

The FKBP52 protein may prevent the Tau protein from turning pathogenic. This may prove significant for the development of new Alzheimer's drugs and for detecting the disease before the onset of clinical symptoms. Etienne Baulieu MD, PhD, the lead author of the investigation, said "There is still a worrying lack of exploration into the causes of age-related brain disorders such as Alzheimer's Disease and dementia. I founded the Institut Baulieu, with the aim of being able to treat and even prevent these diseases. Research on Tau has been very limited, and until recently, I was among the few scientists focusing on Tau pathology. The discovery of the FKBP52 protein is the only ‘anti-Tau’ perspective so far. Its reduced production in the brains of Alzheimer's patients marks a turning point in understanding this complex disease." The study was published in the March 2012, issue of Journal of Alzheimer's Disease.

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Institut National de la Santé et de la Recherche Médicale