Title : A multi-scale view of Alzheimer’s disease: Linking cellular dysfunction to brain activity
Abstract:
Alzheimer’s disease (AD) is a progressive neurodegenerative disorder marked by cognitive decline and widespread cellular dysfunction. While individual pathological features, such as mitochondrial impairment, lysosomal dysfunction, and altered brain activity, have been extensively studied, the interrelationship of these changes across disease progression remains unclear.
This study integrates cellular- and neural-level data to examine how Alzheimer’s disease evolves across multiple biological scales. Using literature-derived measurements of mitochondrial function, lysosomal properties, organelle interactions, and oxidative stress, alongside publicly available electroencephalography (EEG) data, we analyze trends across control, mild cognitive impairment (MCI), early AD, and late AD stages.
We observe a progressive decline in mitochondrial ATP production, increased oxidative stress, and disrupted calcium regulation, accompanied by impaired lysosomal acidification and an increase in lysosome numbers. Altered interactions between mitochondria and the endoplasmic reticulum emerge as a key feature of disease progression, linking metabolic stress to cellular dysfunction.
Age- and sex-dependent analyses reveal distinct trajectories of mitochondrial dysfunction, with males showing stronger age-related increases in oxidative stress and altered organelle coupling. On the neural level, individuals with AD exhibit reduced alpha-band EEG power compared to controls, reflecting disrupted brain network activity.
These findings provide a unified, multi-scale view of Alzheimer’s disease progression, linking intracellular pathology to large-scale neural dysfunction. This framework highlights potential early markers of disease and suggests that targeting mitochondrial health, lysosomal function, and organelle communication may be crucial for future therapeutic strategies.
