Title:Mitochondrial Dysfunction as a Causative Factor in Alzheimer’s Disease-Spectrum Disorders: Lymphocytes as a Window to the Brain
Volume: 18
Issue: 10
关键词:
阿尔茨海默病,神经变性,线粒体,淋巴细胞,大脑,线粒体功能障碍,ROS,遗传学。
摘要: Alzheimer’s disease (AD) is the most common progressive neurodegenerative disease.
Today, AD affects millions of people worldwide and the number of AD cases will further increase
with longer life expectancy. The AD brain is marked by severe neurodegeneration, such as the loss
of synapses and neurons, atrophy and depletion of neurotransmitter systems, especially in the hippocampus
and cerebral cortex. Recent findings highlight the important role of mitochondrial dysfunction
and increased oxidative stress in the pathophysiology of late-onset alzheimer’s disease
(LOAD). These alterations are not only observed in the brain of AD patients but also in the periphery.
In this review, we discuss the potential role of elevated apoptosis, increased oxidative stress
and mitochondrial dysfunction as peripheral markers for the detection of AD in blood cells e.g.
lymphocytes. We evaluate recent findings regarding impaired mitochondrial function comprising
mitochondrial respiration, reduced complex activities of the respiratory chain and altered Mitochondrial
Membrane Potential (MMP) in lymphocytes as well as in neurons. Finally, we will question
whether these mitochondrial parameters might be suitable as an early peripheral marker for the detection
of LOAD but also for the transitional stage between normal aging and Dementia, “Mild
Cognitive Impairment” (MCI).