Potential Diagnostic Value of Red Blood Cells α-Synuclein Heteroaggregates in Alzheimer's Disease

被引：28

作者：

Baldacci, Filippo ^{[1
]}

Daniele, Simona ^{[2
]}

Piccarducci, Rebecca ^{[1
]}

Giampietri, Linda ^{[1
]}

Pietrobono, Deborah ^{[2
]}

Giorgi, Filippo Sean ^{[1
]}

Nicoletti, Valentina ^{[1
]}

Frosini, Daniela ^{[1
]}

Libertini, Paolo ^{[1
]}

Lo Gerfo, Annalisa ^{[1
]}

Petrozzi, Lucia ^{[1
]}

Donadio, Elena ^{[2
]}

Betti, Laura ^{[2
]}

Trincavelli, Maria Letizia ^{[2
]}

Siciliano, Gabriele ^{[1
]}

Ceravolo, Roberto ^{[1
]}

Tognoni, Gloria ^{[1
]}

Bonuccelli, Ubaldo ^{[1
]}

Martini, Claudia ^{[2
]}

机构：

[1] Univ Pisa, Dept Clin & Expt Med, Via Savi 10, I-56126 Pisa, Italy

[2] Univ Pisa, Dept Pharm, Via Bonanno 6, I-56126 Pisa, Italy

来源：

MOLECULAR NEUROBIOLOGY | 2019年 / 56卷 / 09期

关键词：

Alzheimer's disease; alpha-Synuclein; alpha-Synuclein heterocomplexes; beta-Amyloid; Tau; Red blood cells; MILD COGNITIVE IMPAIRMENT; NATIONAL INSTITUTE; ASSOCIATION WORKGROUPS; OXIDATIVE STRESS; A-BETA; PLASMA; TAU; BIOMARKER; GUIDELINES; BRAIN;

D O I：

10.1007/s12035-019-1531-4

中图分类号：

Q189 [神经科学];

学科分类号：

071006 ;

摘要：

A plethora of complex misfolded protein combinations have been found in Alzheimer disease (AD) brains besides the classical pathological hallmarks. Recently, alpha-synuclein (alpha-syn) and its heterocomplexes with amyloid-beta (A beta) and tau have been suggested to be involved in the pathophysiological processes of neurodegenerative diseases. These pathological features are not limited to the brain, but can be also found in peripheral fluids. In this respect, red blood cells (RBCs) have been suggested as a good model to investigate the biochemical alterations of neurodegeneration. Our aim is to find whether RBC concentrations of alpha-syn and its heterocomplexes (i.e., alpha-syn/A beta and alpha-syn/tau) were different in AD patients compared with healthy controls (HC). The levels of homo- and heteroaggregates of alpha-syn, A beta and tau, were analyzed in a cohort of AD patients at early stage either with dementia or prodromal symptoms (N = 39) and age-matched healthy controls (N = 39). All AD patients received a biomarker-based diagnosis (low cerebrospinal fluid levels of A beta peptide combined with high cerebrospinal fluid concentrations of total tau and/or phospho-tau proteins; alternatively, a positivity to cerebral amyloid-PET scan). Our results showed lower concentrations of alpha-syn and its heterocomplexes (i.e., alpha-syn/A beta and alpha-syn/tau) in RBCs of AD patients with respect to HC. RBC alpha-syn/A beta as well as RBC alpha-syn/tau heterodimers discriminated AD participants from HC with fair accuracy, whereas RBC alpha-syn concentrations differentiated poorly the two groups. Although additional investigations are required, these data suggest alpha-syn heteroaggregates in RBCs as potential tool in the diagnostic work-up of early AD diagnosis.

引用

页码：6451 / 6459

页数：9

共 52 条

[21] National Institute on Aging-Alzheimer's Association guidelines for the neuropathologic assessment of Alzheimer's disease [J].

Hyman, Bradley T. ;

Phelps, Creighton H. ;

Beach, Thomas G. ;

Bigio, Eileen H. ;

Cairns, Nigel J. ;

Carrillo, Maria C. ;

Dickson, Dennis W. ;

Duyckaerts, Charles ;

Frosch, Matthew P. ;

Masliah, Eliezer ;

Mirra, Suzanne S. ;

Nelson, Peter T. ;

Schneider, Julie A. ;

Thal, Dietmar Rudolf ;

Thies, Bill ;

Trojanowski, John Q. ;

Vinters, Harry V. ;

Montine, Thomas J. .

ALZHEIMERS & DEMENTIA, 2012, 8 (01) :1-13

[22] Influence of physical exercise on β-amyloid, α-synuclein and tau accumulation: an in vitro model of oxidative stress in human red blood cells [J].

Iofrida, C. ;

Daniele, S. ;

Pietrobono, D. ;

Fusi, J. ;

Galetta, F. ;

Bonuccelli, U. ;

Trincavelli, M. L. ;

Franzoni, F. ;

Martini, C. .

ARCHIVES ITALIENNES DE BIOLOGIE, 2017, 155 (1-2) :33-42

[23] Amyloid β Levels in Human Red Blood Cells [J].

Kiko, Takehiro ;

Nakagawa, Kiyotaka ;

Satoh, Akira ;

Tsuduki, Tsuyoshi ;

Furukawa, Katsutoshi ;

Arai, Hiroyuki ;

Miyazawa, Teruo .

PLOS ONE, 2012, 7 (11)

[24] Non-Alzheimer neurodegenerative pathologies and their combinations are more frequent than commonly believed in the elderly brain: a community-based autopsy series [J].

Kovacs, Gabor G. ;

Milenkovic, Ivan ;

Woehrer, Adelheid ;

Hoeftberger, Romana ;

Gelpi, Ellen ;

Haberler, Christine ;

Hoenigschnabl, Selma ;

Reiner-Concin, Angelika ;

Heinzl, Harald ;

Jungwirth, Susanne ;

Krampla, Wolfgang ;

Fischer, Peter ;

Budka, Herbert .

ACTA NEUROPATHOLOGICA, 2013, 126 (03) :365-384

[25]

Kovacs GG, 2016, INT J MOL SCI, V17, DOI [10.3390/ijms1702089, DOI 10.3390/IJMS1702089]

[26] The peripheral blood of Ab binding RBC as a biomarker for diagnosis of Alzheimer's disease [J].

Lan, Jie ;

Liu, Jinping ;

Zhao, Zhuo ;

Xue, Rong ;

Zhang, Nan ;

Zhang, Peilan ;

Zhao, Peng ;

Zheng, Fang ;

Sun, Xuguo .

AGE AND AGEING, 2015, 44 (03) :458-464

[27] Plasma tau in Alzheimer disease [J].

Mattsson, Niklas ;

Zetterberg, Henrik ;

Janelidze, Shorena ;

Insel, Philip S. ;

Andreasson, Ulf ;

Stomrud, Erik ;

Palmqvist, Sebastian ;

Baker, David ;

Hehir, Cristina A. Tan ;

Jeromin, Andreas ;

Hanlon, David ;

Song, Linan ;

Shaw, Leslie M. ;

Trojanowski, John Q. ;

Weiner, Michael W. ;

Hansson, Oskar ;

Blennow, Kaj .

NEUROLOGY, 2016, 87 (17) :1827-1835

[28] Effects of Baseline CSF α-Synuclein on Regional Brain Atrophy Rates in Healthy Elders, Mild Cognitive Impairment and Alzheimer's Disease [J].

Mattsson, Niklas ;

Insel, Philip ;

Tosun, Duygu ;

Zhang, Jing ;

Jack, Clifford R., Jr. ;

Galasko, Douglas ;

Weiner, Michael .

PLOS ONE, 2013, 8 (12)

[29]

MCKHANN G, 1984, NEUROLOGY, V34, P939, DOI 10.1212/WNL.34.7.939

[30] The diagnosis of dementia due to Alzheimer's disease: Recommendations from the National Institute on Aging-Alzheimer's Association workgroups on diagnostic guidelines for Alzheimer's disease [J].

McKhann, Guy M. ;

Knopman, David S. ;

Chertkow, Howard ;

Hyman, Bradley T. ;

Jack, Clifford R., Jr. ;

Kawas, Claudia H. ;

Klunk, William E. ;

Koroshetz, Walter J. ;

Manly, Jennifer J. ;

Mayeux, Richard ;

Mohs, Richard C. ;

Morris, John C. ;

Rossor, Martin N. ;

Scheltens, Philip ;

Carrillo, Maria C. ;

Thies, Bill ;

Weintraub, Sandra ;

Phelps, Creighton H. .

ALZHEIMERS & DEMENTIA, 2011, 7 (03) :263-269

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