BRAIN BIOCHEMISTRY: METABOLIC CHANGES IN ALZHEIMER'S DISEASE (AD)

Abstract

Alzheimer’s Disease is defined by progressive brain impairment and the presence of multiple molecular abnormalities. We aim to investigate the metabolic changes that occur in both brain tissue and cerebrospinal fluid (CSF) from 30 individuals with AD and 30 healthy individuals of comparable age. We analyzed important indicators of glucose metabolism, mitochondrial function, oxidative stress and neurotransmitter balance through a combination of immunohistochemistry, biochemical methods and metabolomics. Reduced expression of GLUT1 and GLUT3 by 43.2% and 39.6% and a 47.5% decrease in ATP production suggest impaired energy metabolism. The increases in lactate and its ratio to pyruvate indicated that AD brain tissue leaned toward reliance on anaerobic glycolysis. Complex I and Complex IV mitochondrial enzymes showed diminished activity, whereas the level of oxidative stress indicators MDA and 8-OHdG was higher. Our investigation found higher glutamate but lower concentrations of GABA, dopamine, and acetylcholine in the brain. A systematic assessment of metabolites revealed alterations in pathways critical to neuronal function and mitochondrial health. These findings demonstrate that abnormal metabolism is a key contributor to AD development and encourage the use of metabolic markers for earlier diagnosis and possible treatments.