Original Contributions |

Role of Family History for Alzheimer Biomarker Abnormalities in the Adult Children Study

Chengjie Xiong, PhD; Catherine M. Roe, PhD; Virginia Buckles, PhD; Anne Fagan, PhD; David Holtzman, MD; David Balota, PhD; Janet Duchek, PhD; Martha Storandt, PhD; Mark Mintun, MD; Elizabeth Grant, PhD; Abraham Z. Snyder, PhD, MD; Denise Head, PhD; Tammie L. S. Benzinger, MD, PhD; Joseph Mettenburg, MD, PhD; John Csernansky, MD; John C. Morris, MD
Arch Neurol. 2011;68(10):1313-1319. doi:10.1001/archneurol.2011.208.
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Objective To assess whether family history (FH) of Alzheimer disease (AD) alone influences AD biomarker abnormalities.

Design Adult Children Study.

Setting Washington University's Charles F. and Joanne Knight Alzheimer's Disease Research Center.

Participants A total of 269 cognitively normal middle- to older-aged individuals with and without an FH for AD.

Main Outcome Measures Clinical and cognitive measures, magnetic resonance imaging–based brain volumes, diffusion tensor imaging–based white matter microstructure, cerebrospinal fluid biomarkers, and molecular imaging of cerebral fibrillar amyloid with positron emission tomography using the [11C] benzothiazole tracer, Pittsburgh compound B.

Results A positive FH for AD was associated with an age-related decrease of cerebrospinal fluid Aβ42; the ε4 allele of apolipoprotein E (APOE4) did not alter this effect. Age-adjusted cerebrospinal fluid Aβ42 was decreased for individuals with APOE4 compared with the level for those without, and the decrease was larger for individuals with a positive FH compared with the decrease for those without. The variation of cerebrospinal fluid tau and Pittsburgh compound B mean cortical binding potential increased by age. For individuals younger than 55, an age-related increase in mean cortical binding potential was associated with APOE4 but not FH. For individuals older than 55, a positive FH and a positive APOE4 implied the fastest age-related increase in mean cortical binding potential. A positive FH was associated with decreased fractional anisotropy from diffusion tensor imaging in the genu and splenium of the corpus callosum.

Conclusion Independent of APOE4, FH is associated with age-related change of several cerebrospinal fluid, Pittsburgh compound B, and diffusion tensor imaging biomarkers in cognitively normal middle- to older-aged individuals, suggesting that non- APOE susceptibility genes for AD influence AD biomarkers.

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Figure. Cerebrospinal fluid (CSF) Aβ42 as functions of age and family history (FH). See Table 1 for the sample size and demographic characteristics of the subgroup.




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