20 марта 2026
Immunohistochemical Markers of Mitochondrial Electron Transport Chain Instability in Human Brain Regions: A Study of Aging and Alzheimer’s Disease
Baranich Tatiana I., Sukhorukov Vladimir S., Velts Olga V., Voronkov Dmitry N., Shcherbak Ekaterina V., Egorova Anna V., Romanenko Alexander S., Lazarev Dmitry S., Raksha Alexander P., Charyeva Irina G., Yatskovskiy Alexander N., Glinkina Valeria V. and Illarioshkin Sergey N.
Int. J. Mol. Sci. 2026, 27, 2816 https://doi.org/10.3390/ijms27062816
Expanding research indicates that oxidative stress, particularly mitochondrial oxidative
stress, is one of the key components in the pathogenesis of Alzheimer’s disease (AD). Mitochondrial oxidative stress is largely driven by impaired function of electron transport chain
(ETC) complexes and their regulators. This study conducted an immunohistochemical
analysis of ETC proteins (α-subunit of complex V, subunits MTCO1 and MTCO2 of complex
IV) and mitochondrial complex V inhibitor IF-1 in the neurons of the caudate nucleus head,
hippocampus, anterior cingulate gyrus, middle frontal gyrus, and inferior parietal lobule
using autopsy material from patients with sporadic AD. Comparisons were made with
similar brain regions in autopsy material from age-matched elderly patients and young
patients. The results revealed a pattern of ETC impairment in AD fundamentally distinct
from that observed in physiological aging. Specifically, a hippocampus-specific failure of
the adaptive response was identified: unlike other brain regions, compensatory upregulation of ATP synthase does not occur here despite critical reduction in the protective protein
IF-1, directly explaining the heightened vulnerability of hippocampal neurons to damage.
Our data deepen the understanding of AD pathogenesis by highlighting region-specific
mitochondrial defects as promising targets for tailored therapeutic intervention.