Reduced Mitochondrial Activity is Early and Steady in the Entorhinal Cortex but it is Mainly Unmodified in the Frontal Cortex in Alzheimer's Disease

Author(s): Mercedes Armand-Ugon *, Belen Ansoleaga, Sara Berjaoui, Isidro Ferrer *.

Journal Name: Current Alzheimer Research

Volume 14 , Issue 12 , 2017

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Abstract:

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.

Keywords: Alzheimer's disease, mitochondria, mitochondrial phosphorylation, hypometabolism, gene expression, frontal cortex, entorhinal cortex.

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Article Details

VOLUME: 14
ISSUE: 12
Year: 2017
Page: [1327 - 1334]
Pages: 8
DOI: 10.2174/1567205014666170505095921
Price: $58

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