Title:Reduced Mitochondrial Activity is Early and Steady in the Entorhinal Cortex but it is Mainly Unmodified in the Frontal Cortex in Alzheimer's Disease
Volume: 14
Issue: 12
关键词:
阿尔茨海默病，线粒体，线粒体磷酸化，代谢减退，基因表达，额叶皮质，内嗅皮层。
摘要: Background: It is well established that mitochondrial damage plays a role in the pathophysiology
of Alzheimer's disease (AD). However, studies carried out in humans barely contemplate
regional differences with disease progression.
Objective: To study the expression of selected nuclear genes encoding subunits of the mitochondrial
complexes and the activity of mitochondrial complexes in AD, in two regions: the entorhinal cortex
(EC) and frontal cortex area 8 (FC).
Methods: Frozen samples from 148 cases processed for gene expression by qRT-PCR and determination
of individual activities of mitochondrial complexes I, II, IV and V using commercial kits and
home-made assays.
Results: Decreased expression of NDUFA2, NDUFB3, UQCR11, COX7C, ATPD, ATP5L and
ATP50, covering subunits of complex I, II, IV and V, occurs in total homogenates of the EC in AD
stages V-VI when compared with stages I-II. However reduced activity of complexes I, II and V of
isolated mitochondria occurs as early as stages I-II when compared with middle-aged individuals in
the EC. In contrast, no alterations in the expression of the same genes and no alterations in the activity
of mitochondrial complexes are found in the FC in the same series.
Conclusion: Different mechanisms of impaired energy metabolism may occur in AD, one of them,
represented by the EC, is the result of primary and early alteration of mitochondria; the other one is
probably the result, at least in part, of decreased functional input and is represented by hypometabolism
in the FC in AD patients aged 86 or younger.
