[PUBLICATION] Towards early diagnosis of Alzheimer's disease?

Alzheimer's is the most common neurodegenerative dementia syndrome, whose molecular origins, genetic predisposition and therapeutic approach are still debated. Since the 1980s, some studies have shown that fibroblasts and lymphocytes from patients with Alzheimer's disease are sensitive to ionizing radiation, and may present dysfunctions in DNA double-strand break repair systems. Our study aimed to characterize the molecular basis of this radiosensitivity, the signaling and repair of DNA double-strand breaks, the activity of the ATM (Ataxia Telangiectasia Mutated) protein and its transit from the cytoplasm to the nucleus of the cell. The experiments were carried out on fibroblastic lines from Alzheimer's patients (five women and five men) chosen for their characteristic genetic status for Alzheimer's disease, or because they were derived from patients who had first presented symptoms before age 60, with a similar family history.

– Fibroblasts from patients with Alzheimer’s disease all show moderate and significant radiosensitivity associated with a defect in recognizing and repairing DNA double-strand breaks via delayed transit of the ATM protein to the cell nucleus.
– Alzheimer’s fibroblasts spontaneously display a specific abnormal perinuclear localization of the ATM protein, forming a “perinuclear crown” suggesting its aggregation around the cell nucleus.
– Alzheimer’s fibroblasts display a specific protein partnership between the ATM and APOE proteins (the APOE gene is known to be involved in the onset and rapid progression of the disease).
Perinuclear localization of the ATM protein was significantly observed in all the Alzheimer’s disease fibroblast cell lines in our study. It was therefore hypothesized that these perinuclear crowns could serve as a specific biomarker of Alzheimer’s disease, useful for its detection, progression and/or potential treatment. This model has been consolidated by a new mathematical approach and has been patented along with other specific biomarkers by the Neolys Diagnostics team.
Mechanistic model of perinuclear crown formation of pATM protein in fibroblasts from patients with Alzheimer’s disease.

Elise Berthel, R&D Manager – Cellular aging :

➡️ Read the full article here: https://www.mdpi.com/1424-8220/23/5/2614

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