Temporal lobe functional activity and connectivity in young adult APOE e4 carriers

Background—To determine if the APOE e4 allele influences both the functional activation and connectivity of the medial temporal lobes (MTL) during successful memory encoding in young adults. Methods—Twenty-four healthy young adults, twelve carriers and twelve non-carriers of the APOE e4 allele, were scanned in a subsequent memory paradigm, using event-related functional magnetic resonance imaging (fMRI). The neuroanatomical correlates of successful encoding were measured as greater neural activity for subsequently remembered versus forgotten task items, or in short, encoding success activity (ESA). Group differences in ESA within the MTL, as well as whole brain functional connectivity with the MTL, were assessed. Results—In the absence of demographic or performance differences, APOE e4 allele carriers exhibited greater bilateral MTL activity relative to the non-carriers to accomplish the same encoding task. Additionally, while e4 carriers demonstrated greater functional connectivity of ESA-related MTL activity with the posterior cingulate (PCC) and other peri-limbic regions, overall connectivity reductions were found across anterior and posterior cortices. Conclusions—These results suggest that the APOE e4 allele may influence not only functional activations within the MTL, but functional connectivity of the MTL to other regions implicated in memory encoding. Enhanced functional connectivity of the MTL with the PCC in young adult e4 carriers suggests that APOE may be expressed early in brain regions known to be involved in Please address correspondence to: Jeff Browndyke, Ph.D., Functional Imaging & Neurogenomics of Dementia Laboratory, Bryan Alzheimer's Disease Research Center, 2200 West Main Street, Suite A-200, Durham, NC. 27705, (919) 668-1586 voice, (919) 286-3406 fax, [email protected]. *both authors contributed equally to this work. Disclosure: The authors report no conflicts of interest. Publisher's Disclaimer: This is a PDF file of an unedited manuscript that has been accepted for publication. As a service to our customers we are providing this early version of the manuscript. The manuscript will undergo copyediting, typesetting, and review of the resulting proof before it is published in its final citable form. Please note that during the production process errors may be discovered which could affect the content, and all legal disclaimers that apply to the journal pertain. NIH Public Access Author Manuscript Alzheimers Dement. Author manuscript; available in PMC 2011 July 1. Published in final edited form as: Alzheimers Dement. 2010 July ; 6(4): 303–311. doi:10.1016/j.jalz.2009.07.003. N IH PA Athor M anscript N IH PA Athor M anscript N IH PA Athor M anscript Alzheimer's disease long before late-onset dementia is a practical risk or consideration. It is also possible that these functional connectivity differences reflect pleiotropic effects of APOE during early development.