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

被引：48

作者：

Xiong, Chengjie ^{[1
,2
]}

Roe, Catherine M. ^{[2
,3
]}

Buckles, Virginia ^{[2
,3
]}

Fagan, Anne ^{[2
,3
]}

Holtzman, David ^{[2
,3
,9
]}

Balota, David ^{[2
,7
]}

Duchek, Janet ^{[2
,7
]}

Storandt, Martha ^{[2
,3
,7
]}

Mintun, Mark ^{[2
,8
]}

Grant, Elizabeth ^{[1
,2
]}

Snyder, Abraham Z. ^{[2
,8
]}

Head, Denise ^{[2
,7
,8
]}

Benzinger, Tammie L. S. ^{[2
,8
]}

Mettenburg, Joseph ^{[2
,8
]}

Csernansky, John ^{[2
,10
,11
,12
]}

Morris, John C. ^{[2
,3
,4
,5
,6
]}

机构：

[1] Washington Univ, Sch Med, Dept Biostat, St Louis, MO 63110 USA

[2] Washington Univ, Sch Med, Charles F & Joanne Knight Alzheimers Dis Res Ctr, St Louis, MO 63110 USA

[3] Washington Univ, Sch Med, Dept Neurol, St Louis, MO 63110 USA

[4] Washington Univ, Sch Med, Dept Pathol & Immunol, St Louis, MO 63110 USA

[5] Washington Univ, Sch Med, Dept Phys Therapy, St Louis, MO 63110 USA

[6] Washington Univ, Sch Med, Dept Occupat Therapy, St Louis, MO 63110 USA

[7] Washington Univ, Sch Med, Dept Psychol, St Louis, MO 63110 USA

[8] Washington Univ, Sch Med, Dept Radiol, St Louis, MO 63110 USA

[9] Washington Univ, Sch Med, Dept Dev Biol, St Louis, MO 63110 USA

[10] Stone Inst Psychiat, Dept Psychiat, Chicago, IL USA

[11] Stone Inst Psychiat, Dept Behav Sci, Chicago, IL USA

[12] NW Mem Hosp, Chicago, IL 60611 USA

来源：

ARCHIVES OF NEUROLOGY | 2011年 / 68卷 / 10期

关键词：

CEREBROSPINAL-FLUID A-BETA(42); MILD COGNITIVE IMPAIRMENT; GENOME-WIDE ASSOCIATION; IDENTIFIES VARIANTS; NORMAL INDIVIDUALS; WORKING-MEMORY; DEMENTIA; DISEASE; RELIABILITY; DECLINE;

D O I：

10.1001/archneurol.2011.208

中图分类号：

R74 [神经病学与精神病学];

学科分类号：

摘要：

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 [C-11] benzothiazole tracer, Pittsburgh compound B. Results: A positive FH for AD was associated with an age-related decrease of cerebrospinal fluid A beta 42; the epsilon 4 allele of apolipoprotein E (APOE4) did not alter this effect. Age-adjusted cerebrospinal fluid A beta 42 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.

引用

页码：1313 / 1319

页数：7

共 60 条

[11] Cerebrospinal fluid tau and ptau181 increase with cortical amyloid deposition in cognitively normal individuals: Implications for future clinical trials of Alzheimer's disease [J].