title: A combined effect of two Alzheimer's risk genes on medial temporal activity during executive attention in young adults.
abstract: A recent history of failed clinical trials suggests that waiting until even the early stages of onset of Alzheimer's disease may be too late for effective treatment, pointing to the importance of early intervention in young people. Early intervention will require markers of Alzheimer's risk that track with genotype but are capable of responding to treatment. Here, we sought to identify a functional MRI signature of combined Alzheimer's risk imparted by two genetic risk factors. We used a task of executive attention during fMRI in participants genotyped for two Alzheimer's risk alleles: APOE-ε4 and CLU-C. Executive attention is a sensitive indicator of the progression of Alzheimer's even in the early stages of mild cognitive impairment, but has not yet been investigated as a marker of Alzheimer's risk in young adults. Functional MRI revealed that APOE-ε4 and CLU-C had an additive effect on brain activity such that increased combined genetic risk was associated with decreased brain activity during executive attention, including in the medial temporal lobe, a brain area affected early in Alzheimer's pathogenesis.
authors.affiliation: Department of Psychology, Georgetown University, 37th and O Streets, NW, 302-C White-Gravenor, Washington, DC 20057, United States. Electronic address: aeg58@georgetown.edu.
authors.forename: Adam E
authors.initials: AE
authors.lastname: Green
authors.affiliation: Department of Psychology, Michigan State University, East Lansing, MI, United States.
authors.forename: Jeremy R
authors.initials: JR
authors.lastname: Gray
authors.affiliation: Department of Psychology, University of Minnesota, Minneapolis, MN, United States.
authors.forename: Colin G
authors.initials: CG
authors.lastname: Deyoung
authors.affiliation: Department of Neuroscience, Georgetown University Medical Center, Washington, DC, United States.
authors.forename: Timothy R
authors.initials: TR
authors.lastname: Mhyre
authors.affiliation: Department of Neuroscience, Georgetown University Medical Center, Washington, DC, United States.
authors.forename: Robert
authors.initials: R
authors.lastname: Padilla
authors.affiliation: Department of Psychology, Georgetown University, 37th and O Streets, NW, 302-C White-Gravenor, Washington, DC 20057, United States; Department of Neuroscience, Georgetown University Medical Center, Washington, DC, United States.
authors.forename: Amanda M
authors.initials: AM
authors.lastname: Dibattista
authors.affiliation: Department of Neuroscience, Georgetown University Medical Center, Washington, DC, United States.
authors.forename: G
authors.initials: G
authors.lastname: William Rebeck
mesh_terms: D000293:Adolescent; D000328:Adult; D000704:Analysis of Variance; D053327:Apolipoprotein E4 / Q000235:genetics*; D001288:Attention / Q000502:physiology*; D051152:Clusterin / Q000235:genetics*; D056344:Executive Function / Q000502:physiology*; D005260:Female; D005838:Genotype; D006801:Humans; D007091:Image Processing, Computer-Assisted; D008279:Magnetic Resonance Imaging; D008297:Male; D009483:Neuropsychological Tests; D010100:Oxygen / Q000097:blood; D013702:Temporal Lobe / Q000098:blood supply*; D055815:Young Adult
chemical_list: D053327:Apolipoprotein E4; C495242:CLU protein, human; D051152:Clusterin; D010100:Oxygen
keywords: APOE; CLU; Executive attention; Medial temporal lobe; fMRI