Aims

Besides the two main Alzheimer’s disease (AD) hallmarks (neurofibrillary tangles and senile plaques), the alteration of the structure and function of mitochondria was shown to be linked to the toxicity of Aβ peptides, in particular through the increase of reactive oxygen species (ROS) production. Furthermore, we have recently shown that APP C-terminal fragments (C83 and C99) localize to mitochondria-associated membranes (1) and trigger mitochondrial dysfunctions, overproduction of ROS and blockade of the mitophagy process (2).

Aims : We assessed mitochondrial structure and function and analyzed mitophagy markers in a cohort of fibroblasts isolated from sporadic AD patients.

Methods

We used fibroblasts from control, mild-cognitive impairment (MCI), or AD (AD) patients. Mitochondrial cristae organization as well as area, perimeter and number were quantified by electron microscopy. Measurements of mitochondrial ROS production and mitochondrial potential were analyzed by flow cytometry. The expression of proteins involved in mitophagy and mitochondrial dynamics were evaluated by SDS-PAGE.

Results

Fibroblasts from AD patients exhibit disorganization of mitochondria cristae ultrastructure with an increase of size in comparison of control and MCI cells. Electronic microscopy analyses also reveal an enlargement of endosomes in AD fibroblasts. Furthermore, mitochondrial function is also disrupted with an alteration of the mitochondrial membrane potential and modifications of expression of mitophagy markers.

Conclusions

Altogether, our data highlight mitochondria impairment in peripheral cells of AD patients and emphasize their potential use in AD diagnosis and personalized medicine.

(1) Del Prete D, et al. JAD 2017.

(2) Vaillant-Beuchot L^#, Mary A^#, et al. Under revision, Acta Neuropathologica.