In vivoPET imaging studies of young-adult carriers of the apolipoprotein E ε4 allele (APOEε4), 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 APOEε4. At-risk ε4 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 ε4 homozygote, the ε4 carriers did not have increased soluble amyloid-β, histologic amyloid-β, 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.

Multiciliated ependymal (E1) cells line the brain ventricles and are essential for brain homeostasis. We previously identified in the lateral ventricles a rare ependymal subpopulation (E2) with only two cilia and unique basal bodies. Here we show that E2 cells form a distinct biciliated epithelium extending along the ventral third into the fourth ventricle. In the third ventricle floor, apical profiles with only primary cilia define an additional uniciliated (E3) epithelium. E2 and E3 cells' ultrastructure, marker expression and basal processes indicate that they correspond to subtypes of tanycytes. Using sonic hedgehog lineage tracing, we show that the third and fourth ventricle E2 and E3 epithelia originate from the anterior floor plate. E2 and E3 cells complete their differentiation 2–3 weeks after birth, suggesting a link to postnatal maturation. These data reveal discrete bands of E2 and E3 cells that may relay information from the CSF to underlying neural circuits along the ventral midline.