Association of prion protein with cognitive functioning in humans

被引：11

作者：

Breitling, Lutz Philipp ^{[1
]}

Mueller, Heiko ^{[1
]}

Stegmaier, Christa ^{[2
]}

Kliegel, Matthias ^{[3
]}

Brenner, Hermann ^{[1
]}

机构：

[1] German Canc Res Ctr, Div Clin Epidemiol & Aging Res, D-6900 Heidelberg, Germany

[2] Saarland Canc Registry, Saarbrucken, Germany

[3] Univ Geneva, Dept Psychol, CH-1211 Geneva 4, Switzerland

来源：

EXPERIMENTAL GERONTOLOGY | 2012年 / 47卷 / 12期

关键词：

Prion protein; Epidemiological study; Homo sapiens; Cognition; Executive function; AMYLOID-BETA OLIGOMERS; ALZHEIMERS-DISEASE; IMPAIRMENT; INHIBITION; MOUSE; PRPC;

D O I：

10.1016/j.exger.2012.08.001

中图分类号：

R592 [老年病学]; C [社会科学总论];

学科分类号：

03 ; 0303 ; 100203 ;

摘要：

Objectives: Recent animal studies have suggested a key role for cellular prion protein (PrPc) in the pathological consequences of amyloid plaque formation, the hallmark of Alzheimer's disease. This epidemiological study investigated whether serum concentrations of PrPc are associated with cognitive functioning in humans. Design, Setting, Participants: Cross-sectional study of 1,322 participants from the elderly general population in Germany, aged 65 + years at baseline (2000-2002). Measurements: Cognitive functioning was assessed by the COGTEL phone interview 5 years after baseline. Serum PrPc was determined by a commercial immunoassay. Results: In multiple linear regression adjusted for important confounders, subjects in higher PrPc quintiles appeared to have lower cognitive functioning scores than those in the lowest PrPc quintile. Spline regression suggested pronounced non-linearity with an inverse association between PrPc and cognitive functioning levelling off beyond median PrPc. Cognitive subdomain-specific models produced somewhat heterogeneous results. Conclusion: The findings are suggestive of an independent association of PrPc with cognitive functioning in humans. Confirmatory and longitudinal studies are needed to elucidate the potential of PrPc for applications in early risk stratification for cognitive impairment. (C) 2012 Elsevier Inc. All rights reserved.

引用

页码：919 / 924

页数：6

共 31 条

[1] The prion's elusive reason for being [J].

Aguzzi, Adriano ;

Baumann, Frank ;

Bremer, Jullane .

ANNUAL REVIEW OF NEUROSCIENCE, 2008, 31 :439-477

[2] Aβ Inhibition of Ionic Conductance in Mouse Basal Forebrain Neurons Is Dependent upon the Cellular Prion Protein PrPC [J].

Alier, Kwai ;

Ma, Li ;

Yang, Jing ;

Westaway, David ;

Jhamandas, Jack H. .

JOURNAL OF NEUROSCIENCE, 2011, 31 (45) :16292-16297

[3] Synthetic amyloid-β oligomers impair long-term memory independently of cellular prion protein [J].

Balducci, Claudia ;

Beeg, Marten ;

Stravalaci, Matteo ;

Bastone, Antonio ;

Sclip, Alessandra ;

Biasini, Emiliano ;

Tapella, Laura ;

Colombo, Laura ;

Manzoni, Claudia ;

Borsello, Tiziana ;

Chiesa, Roberto ;

Gobbi, Marco ;

Salmona, Mario ;

Forloni, Gianluigi .

PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 2010, 107 (05) :2295-2300

[4] Alzheimer's Disease Brain-Derived Amyloid-β-Mediated Inhibition of LTP In Vivo Is Prevented by Immunotargeting Cellular Prion Protein [J].

Barry, Andrew E. ;

Klyubin, Igor ;

Mc Donald, Jessica M. ;

Mably, Alexandra J. ;

Farrell, Michael A. ;

Scott, Michael ;

Walsh, Dominic M. ;

Rowan, Michael J. .

JOURNAL OF NEUROSCIENCE, 2011, 31 (20) :7259-7263

[5] Amyloid-β-induced Synapse Damage Is Mediated via Cross-linkage of Cellular Prion Proteins [J].

Bate, Clive ;

Williams, Alun .

JOURNAL OF BIOLOGICAL CHEMISTRY, 2011, 286 (44) :37955-37963

[6] Mild cognitive impairment - a review of prevalence, incidence and outcome according to current approaches [J].

Bischkopf, J ;

Busse, A ;

Angermeyer, MC .

ACTA PSYCHIATRICA SCANDINAVICA, 2002, 106 (06) :403-414

[7] Large-Scale Application of a Telephone-Based Test of Cognitive Functioning in Older Adults [J].

Breitling, Lutz P. ;

Wolf, Melanie ;

Mueller, Heiko ;

Raum, Elke ;

Kliegel, Matthias ;

Brenner, Hermann .

DEMENTIA AND GERIATRIC COGNITIVE DISORDERS, 2010, 30 (04) :309-316

[8] Anti-PrPC monoclonal antibody infusion as a novel treatment for cognitive deficits in an alzheimer's disease model mouse [J].

Chung, Erika ;

Ji, Yong ;

Sun, Yanjie ;

Kascsak, Richard J. ;

Kascsak, Regina B. ;

Mehta, Pankaj D. ;

Strittmatter, Stephen M. ;

Wisniewski, Thomas .

BMC NEUROSCIENCE, 2010, 11

[9] ALZHEIMER'S DISEASE A prion protein connection [J].

Cisse, Moustapha ;

Mucke, Lennart .

NATURE, 2009, 457 (7233) :1090-1091

[10]

Crawford J.R., 2005, The Effectiveness of Rehabilitation for Cognitive Deficits, P233

← 1 2 3 4 →