Reduced Posterior Cingulate Mitochondrial Activity in Expired Young Adult Carriers of the APOE epsilon 4 Allele, the Major Late-Onset Alzheimer's Susceptibility Gene

作者：Valla Jon^*; Yaari Roy; Wolf Andrew B; Kusne Yael; Beach Thomas G; Roher Alex E; Corneveaux Jason J; Huentelman Matthew J; Caselli Richard J; Reiman Eric M

来源：Journal of Alzheimer's Disease, 2010, 22(1): 307-313.

DOI：10.3233/JAD-2010-100129

• Alzheimer's etiology
• bioenergetics
• biomarkers
• cytochrome c oxidase
• differential vulnerability
• neocortex

In vivo PET imaging studies of young-adult carriers of the apolipoprotein E epsilon 4 allele (APOE epsilon 4), the major Alzheimer's disease (AD) susceptibility gene, have demonstrated declines in glucose metabolism in brain areas later vulnerable to AD, such as posterior cingulate cortex, decades before the possible onset of symptoms. We have previously shown in postmortem studies that such metabolic declines in AD are associated with brain regional mitochondrial dysfunction. To determine whether young adult at-risk individuals demonstrate similar mitochondrial functional decline, we histochemically assessed postmortem tissues from the posterior cingulate cortex of young-adult carriers and noncarriers of APOE epsilon 4. At-risk epsilon 4 carriers had lower mitochondrial cytochrome oxidase activity than noncarriers in posterior cingulate cortex, particularly within the superficial cortical lamina, a pattern similar to that seen in AD patients. Except for one 34 year-old epsilon 4 homozygote, the epsilon 4 carriers did not have increased soluble amyloid-beta, histologic amyloid-beta, or tau pathology in this same region. This functional biomarker may prove useful in early detection and tracking of AD and indicates that mitochondrial mechanisms may contribute to the predisposition to AD before any evidence of amyloid or tau pathology.

• 出版日期2010