Spatiotemporal Complexity of Fibroblast Networks Screens for Alzheimer's Disease

被引:5
作者
Chirila, Florin V. [1 ]
Khan, Tapan K. [1 ]
Alkon, Daniel L. [1 ]
机构
[1] Blanchette Rockefeller Neurosci Inst, Morgantown, WV USA
关键词
Alzheimer disease; biomarkers; cell aggregation; cell migration; diagnosis; fractal dimension; lacunarity; networks; AMYLOID BETA-PROTEIN; SKIN FIBROBLASTS; FRACTAL DIMENSION; MUTATION; ACETYLCHOLINESTERASE; PRESENILIN-1; DYSFUNCTION; ACTIVATION; DEPOSITION; EXPRESSION;
D O I
10.3233/JAD-2012-120745
中图分类号
Q189 [神经科学];
学科分类号
071006 ;
摘要
Drugs to treat Alzheimer's disease (AD) have been unsuccessful in preventing its devastating cognitive deficits and progressive neurodegeneration. The lack of a definitive diagnostic for AD has been a major obstacle to AD drug discovery. Here, we describe a novel, highly accurate peripheral diagnostic for AD patients based on quantitatively measured complexity of skin-sampled fibroblast networks. A significant number of samples were studied under double-blind conditions and had autopsy and/or genetic validation. An additional sample confirmed the diagnostic discrimination on freshly obtained skin samples. A sub-sample of these diagnostic differences were induced by oligomerized amyloid-beta(1-42). Based on the accuracy of these measures that utilize physical principles such as fractal dimension and lacunarity as well as the significant correlation with disease duration, this biomarker profile appears to identify accurately AD patients for therapeutic intervention.
引用
收藏
页码:165 / 176
页数:12
相关论文
共 50 条
[1]   Skin nervous system interactions [J].
Ansel, JC ;
Kaynard, AH ;
Armstrong, CA ;
Olerud, J ;
Bunnett, N ;
Payan, D .
JOURNAL OF INVESTIGATIVE DERMATOLOGY, 1996, 106 (01) :198-204
[2]   Differences in extracellular matrix production and basic fibroblast growth factor response in skin fibroblasts from sporadic and familial Alzheimer's disease [J].
Bellucci, Catia ;
Lilli, Cinzia ;
Baroni, Tiziano ;
Parnetti, Lucilla ;
Sorbi, Sandro ;
Emiliani, Carla ;
Lumare, Eleonora ;
Calabresi, Paolo ;
Balloni, Stefania ;
Bodo, Maria .
MOLECULAR MEDICINE, 2007, 13 (9-10) :542-550
[3]   Saliva levels of Abeta1-42 as potential biomarker of Alzheimer's disease: a pilot study [J].
Bermejo-Pareja, Felix ;
Antequera, Desiree ;
Vargas, Teo ;
Molina, Jose A. ;
Carro, Eva .
BMC NEUROLOGY, 2010, 10 :108
[4]  
Brandan E, 1996, J CLIN PATHOL-CL MOL, V49, pM351
[5]   Increased susceptibility to amyloid toxicity in familial Alzheimer's fibroblasts [J].
Cecchi, Cristina ;
Fiorillo, Claudia ;
Baglioni, Serena ;
Pensalfini, Anna ;
Bagnoli, Silvia ;
Nacmias, Benedetta ;
Sorbi, Sandro ;
Nosi, Daniele ;
Relini, Annalisa ;
Liguri, Gianfranco .
NEUROBIOLOGY OF AGING, 2007, 28 (06) :863-876
[6]   Development of gerbil medial superior olive: integration of temporally delayed excitation and inhibition at physiological temperature [J].
Chirila, Florin V. ;
Rowland, Kevin C. ;
Thompson, Jesse M. ;
Spirou, George A. .
JOURNAL OF PHYSIOLOGY-LONDON, 2007, 584 (01) :167-190
[7]   EXCESSIVE PRODUCTION OF AMYLOID BETA-PROTEIN BY PERIPHERAL CELLS OF SYMPTOMATIC AND PRESYMPTOMATIC PATIENTS CARRYING THE SWEDISH FAMILIAL ALZHEIMER-DISEASE MUTATION [J].
CITRON, M ;
VIGOPELFREY, C ;
TEPLOW, DB ;
MILLER, C ;
SCHENK, D ;
JOHNSTON, J ;
WINBLAD, B ;
VENIZELOS, N ;
LANNFELT, L ;
SELKOE, DJ .
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 1994, 91 (25) :11993-11997
[8]  
Eckert A, 1998, J NEURAL TRANSM-SUPP, P259
[9]   POTASSIUM CHANNEL DYSFUNCTION IN FIBROBLASTS IDENTIFIES PATIENTS WITH ALZHEIMER-DISEASE [J].
ETCHEBERRIGARAY, R ;
ITO, E ;
OKA, K ;
TOFELGREHL, B ;
GIBSON, GE ;
ALKON, DL .
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 1993, 90 (17) :8209-8213
[10]   Therapeutic effects of PKC activators in Alzheimer's disease transgenic mice [J].
Etcheberrigaray, R ;
Tan, M ;
Dewachter, I ;
Kuipéri, C ;
Van der Auwera, I ;
Wera, S ;
Qiao, LX ;
Bank, B ;
Nelson, TJ ;
Kozikowski, AP ;
Van Leuven, F ;
Alkon, DL .
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 2004, 101 (30) :11141-11146