Human fibroblasts from sporadic Alzheimer's disease (AD) patients show mitochondrial alterations and lysosome...

Area of Science:

• Cell Biology
• Neuroscience
• Mitochondrial Biology

Background:

• Mitophagy is crucial for mitochondrial health and preventing neurodegeneration.
• Alzheimer's disease (AD) is linked to mitochondrial dysfunction and aging.
• Understanding cellular mechanisms in sporadic AD (sAD) is vital.

Purpose of the Study:

• To investigate mitochondrial ROS, function, and mitophagy in sAD fibroblasts.
• To explore lysosomal function and degradation capacity in sAD.
• To assess the impact of nicotinamide riboside on these pathways.

Main Methods:

• Primary fibroblast cultures from sAD patients and healthy controls.
• Assessment of mitochondrial reactive oxygen species (ROS) levels.
• Analysis of mitochondrial morphology, bioenergetics, autophagy, mitophagy, and lysosomal degradation.

Main Results:

• sAD fibroblasts exhibit increased mitochondrial ROS, altered morphology, and impaired bioenergetics.
• Defects in autophagy, mitophagy, and lysosome-mediated degradation were found in sAD cells.
• Lysosomal degradation capacity was reduced in sAD fibroblasts, despite high lysosome abundance.
• Nicotinamide riboside decreased mitochondrial ROS but did not improve lysosomal degradation in sAD cells.

Conclusions:

• Dysregulation of lysosome and autophagy/mitophagy pathways contributes to sAD pathogenesis.
• Mitochondrial dysfunction and impaired cellular clearance mechanisms are key features of sAD.
• Targeting these pathways may offer therapeutic potential for sAD.