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

[ Vol. 14 , Issue. 12 ]

Author(s):

Mercedes Armand-Ugon *, Belen Ansoleaga, Sara Berjaoui and Isidro Ferrer *   Pages 1327 - 1334 ( 8 )

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.

Affiliation:

Institute of Neuropathology, Service of Pathologic Anatomy, Bellvitge University Hospital, carrer Feixa Llarga s/n, 08907 Hospitalet de Llobregat, Barcelona, Institute of Neuropathology, IDIBELL-Bellvitge University Hospital, University of Barcelona, Hospitalet de Llobregat; CIBERNED (Centro de Investigacion Biomedica en Red de Enfermedades Neurodegenerativas), Institute of Neuropathology, IDIBELL-Bellvitge University Hospital, University of Barcelona, Hospitalet de Llobregat; CIBERNED (Centro de Investigacion Biomedica en Red de Enfermedades Neurodegenerativas), Institute of Neuropathology, Service of Pathologic Anatomy, Bellvitge University Hospital, carrer Feixa Llarga s/n, 08907 Hospitalet de Llobregat, Barcelona



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