Accumulation of high molecular weight kininogen in the brains of Alzheimer's disease patients may affect microglial function by altering phagocytosis and lysosomal cathepsin activity.
Alzheimer's disease
cathepsin
high molecular weight kininogen
microglia
phagocytosis
Journal
Alzheimer's & dementia : the journal of the Alzheimer's Association
ISSN: 1552-5279
Titre abrégé: Alzheimers Dement
Pays: United States
ID NLM: 101231978
Informations de publication
Date de publication:
10 2022
10 2022
Historique:
revised:
14
09
2021
received:
11
03
2021
accepted:
14
10
2021
pubmed:
4
1
2022
medline:
21
10
2022
entrez:
3
1
2022
Statut:
ppublish
Résumé
Increased activation of the contact system protein high molecular weight kininogen (HK) has been shown in plasma and cerebrospinal fluid of Alzheimer's disease (AD) patients, but its potential role in the brain has not been explored. We assessed HK levels in brain tissue from 20 AD patients and controls and modeled the effects of HK on microglia-like cells in culture. We show increased levels of HK in the hippocampus of AD patients, which colocalized with amyloid beta (Aβ) deposits and activated microglia. Treatment of microglia with HK led to cell clustering and elevated levels of phagocytosed Aβ. We demonstrate that microglia internalize HK and traffic it to lysosomes, which is accompanied by reduced activity of lysosomal cathepsins L and S. Our results suggest that HK accumulation in the AD hippocampus may alter microglial uptake and degradation of Aβ fibrils, possibly contributing to microglial dysfunction in AD.
Substances chimiques
Amyloid beta-Peptides
0
Cathepsins
EC 3.4.-
Kininogen, High-Molecular-Weight
0
Types de publication
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Pagination
1919-1929Informations de copyright
© 2021 the Alzheimer's Association.
Références
Lalmanach G, Naudin C, Lecaille F, Fritz H. Kininogens: more than cysteine protease inhibitors and kinin precursors. Biochimie. 2010;92:1568-1579.
Chavakis T, Kanse SM, Pixley RA, et al. Regulation of leukocyte recruitment by polypeptides derived from high molecular weight kininogen. FASEB J. 2001;15:2365-2376.
Barbasz A, Guevara-Lora I, Rapala-Kozik M, Kozik A. Kininogen binding to the surfaces of macrophages. Int Immunopharmacol. 2008;8:211-216.
Khan MM, Bradford HN, Isordia-Salas I, et al. High-molecular-weight kininogen fragments stimulate the secretion of cytokines and chemokines through uPAR, Mac-1, and gC1qR in monocytes. Arterioscler Thromb Vasc Biol. 2006;26:2260-2266.
Zamolodchikov D, Chen ZL, Conti BA, Renne T, Strickland S. Activation of the factor XII-driven contact system in Alzheimer's disease patient and mouse model plasma. Proc Natl Acad Sci U S A. 2015;112:4068-4073.
Chen ZL, Revenko AS, Singh P, MacLeod AR, Norris EH, Strickland S. Depletion of coagulation factor XII ameliorates brain pathology and cognitive impairment in Alzheimer disease mice. Blood. 2017;129:2547-2556.
Singh PK, Chen ZL, Ghosh D, Strickland S, Norris EH. Increased plasma bradykinin level is associated with cognitive impairment in Alzheimer's patients. Neurobiol Dis. 2020;139:104833.
Zamolodchikov D, Renne T, Strickland S. The Alzheimer's disease peptide beta-amyloid promotes thrombin generation through activation of coagulation factor XII. J Thromb Haemost. 2016;14:995-1007.
Shibayama Y, Joseph K, Nakazawa Y, Ghebreihiwet B, Peerschke EI, Kaplan AP. Zinc-dependent activation of the plasma kinin-forming cascade by aggregated beta amyloid protein. Clin Immunol. 1999;90:89-99.
Bergamaschini L, Donarini C, Foddi C, Gobbo G, Parnetti L, Agostoni A. The region 1-11 of Alzheimer amyloid-beta is critical for activation of contact-kinin system. Neurobiol Aging. 2001;22:63-69.
Maas C, Govers-Riemslag JW, Bouma B, et al. Misfolded proteins activate factor XII in humans, leading to kallikrein formation without initiating coagulation. J Clin Invest. 2008;118:3208-3218.
Yasuhara O, Walker DG, McGeer PL. Hageman factor and its binding sites are present in senile plaques of Alzheimer's disease. Brain Res. 1994;654:234-240.
Ashby EL, Love S, Kehoe PG. Assessment of activation of the plasma kallikrein-kinin system in frontal and temporal cortex in Alzheimer's disease and vascular dementia. Neurobiol Aging. 2012;33:1345-1355.
Walker DG, Yasuhara O, Patston PA, McGeer EG, McGeer PL. Complement C1 inhibitor is produced by brain tissue and is cleaved in Alzheimer disease. Brain Res. 1995;675:75-82.
Bergamaschini L, Parnetti L, Pareyson D, Canziani S, Cugno M, Agostoni A. Activation of the contact system in cerebrospinal fluid of patients with Alzheimer disease. Alzheimer Dis Assoc Disord. 1998;12:102-108.
Bhoola KD, Figueroa CD, Worthy K. Bioregulation of kinins: kallikreins, kininogens, and kininases. Pharmacol Rev. 1992;44:1-80.
Condello C, Yuan P, Schain A, Grutzendler J. Microglia constitute a barrier that prevents neurotoxic protofibrillar Abeta42 hotspots around plaques. Nat Commun. 2015;6:6176.
Brendza RP, Holtzman DM. Amyloid-beta immunotherapies in mice and men. Alzheimer Dis Assoc Disord. 2006;20:118-123.
van Dyck CH. Anti-amyloid-beta monoclonal antibodies for Alzheimer's disease: pitfalls and promise. Biol Psychiatry. 2018;83:311-319.
Baik SH, Kang S, Son SM, Mook-Jung I. Microglia contributes to plaque growth by cell death due to uptake of amyloid beta in the brain of Alzheimer's disease mouse model. Glia. 2016;64:2274-2290.
Streit WJ, Braak H, Xue QS, Bechmann I. Dystrophic (senescent) rather than activated microglial cells are associated with tau pathology and likely precede neurodegeneration in Alzheimer's disease. Acta Neuropathol. 2009;118:475-485.
Sanchez-Mejias E, Navarro V, Jimenez S, et al. Soluble phospho-tau from Alzheimer's disease hippocampus drives microglial degeneration. Acta Neuropathol. 2016;132:897-916.
Krasemann S, Madore C, Cialic R, et al. The TREM2-APOE pathway drives the transcriptional phenotype of dysfunctional microglia in neurodegenerative diseases. Immunity. 2017;47:566-581.e569.
Chen ZL, Singh P, Wong J, Horn K, Strickland S, Norris EH. An antibody against HK blocks Alzheimer's disease peptide beta-amyloid-induced bradykinin release in human plasma. Proc Natl Acad Sci U S A. 2019;116:22921-22923.
Fu H, Liu B, Frost JL, et al. Complement component C3 and complement receptor type 3 contribute to the phagocytosis and clearance of fibrillar Abeta by microglia. Glia. 2012;60:993-1003.
Muller-Esterl W. Novel functions of the kininogens. Semin Thromb Hemost. 1987;13:115-126.
Turk B, Stoka V, Turk V, :Johansson G, Cazzulo JJ, Björk I. High-molecular-weight kininogen binds two molecules of cysteine proteinases with different rate constants. FEBS Lett. 1996;391:109-112.
Jung M, Lee J, Seo HY, Lim JS, Kim EK. Cathepsin inhibition-induced lysosomal dysfunction enhances pancreatic beta-cell apoptosis in high glucose. PLoS One. 2015;10:e0116972.
Cermak S, Kosicek M, Mladenovic-Djordjevic A, Smiljanic K, Kanazir S, Hecimovic S. Loss of cathepsin B and L leads to lysosomal dysfunction, NPC-like cholesterol sequestration and accumulation of the key Alzheimer's proteins. PLoS One. 2016;11:e0167428.
Raskin J, Cummings J, Hardy J, Schuh K, Dean RA. Neurobiology of Alzheimer's disease: integrated molecular, physiological, anatomical, biomarker, and cognitive dimensions. Curr Alzheimer Res. 2015;12:712-722.
Neth P, Arnhold M, Nitschko H, Fink E. The mRNAs of prekallikrein, factors XI and XII, and kininogen, components of the contact phase cascade are differentially expressed in multiple non-hepatic human tissues. Thromb Haemost. 2001;85:1043-1047.
Zipser BD, Johanson CE, Gonzalez L, et al. Microvascular injury and blood-brain barrier leakage in Alzheimer's disease. Neurobiol Aging. 2007;28:977-986.
Viggars AP, Wharton SB, Simpson JE, et al. Alterations in the blood brain barrier in ageing cerebral cortex in relationship to Alzheimer-type pathology: a study in the MRC-CFAS population neuropathology cohort. Neurosci Lett. 2011;505:25-30.
Cortes-Canteli M, Mattei L, Richards AT, Norris EH, Strickland S. Fibrin deposited in the Alzheimer's disease brain promotes neuronal degeneration. Neurobiol Aging. 2015;36:608-617.
Cortes-Canteli M, Zamolodchikov D, Ahn HJ, Strickland S, Norris EH. Fibrinogen and altered hemostasis in Alzheimer's disease. J Alzheimers Dis. 2012;32:599-608.
Montagne A, Barnes SR, Sweeney MD, et al. Blood-brain barrier breakdown in the aging human hippocampus. Neuron. 2015;85:296-302.
Stephan BC, Matthews FE, Ma B, et al. Alzheimer and vascular neuropathological changes associated with different cognitive States in a non-demented sample. J Alzheimers Dis. 2012;29:309-318.
McAleese KE, Graham S, Dey M, et al. Extravascular fibrinogen in the white matter of Alzheimer's disease and normal aged brains: implications for fibrinogen as a biomarker for Alzheimer's disease. Brain Pathol. 2019;29:414-424.
Price JL, Morris JC. Tangles and plaques in nondemented aging and “preclinical” Alzheimer's disease. Ann Neurol. 1999;45:358-368.
Sengillo JD, Winkler EA, Walker CT, Sullivan JS, Johnson M, Zlokovic BV. Deficiency in mural vascular cells coincides with blood-brain barrier disruption in Alzheimer's disease. Brain Pathol. 2013;23:303-310.
Arai T, Miklossy J, Klegeris A, Guo JP, McGeer PL. Thrombin and prothrombin are expressed by neurons and glial cells and accumulate in neurofibrillary tangles in Alzheimer disease brain. J Neuropathol Exp Neurol. 2006;65:19-25.
Yin X, Wright J, Wall T, Grammas P. Brain endothelial cells synthesize neurotoxic thrombin in Alzheimer's disease. Am J Pathol. 2010;176:1600-1606.
Takano M, Horie M, Yayama K, Okamoto H. Lipopolysaccharide injection into the cerebral ventricle evokes kininogen induction in the rat brain. Brain Res. 2003;978:72-82.
Richoux JP, Gelly JL, Bouhnik J, et al. The kallikrein-kinin system in the rat hypothalamus. Immunohistochemical localization of high molecular weight kininogen and T kininogen in different neuronal systems. Histochemistry. 1991;96:229-243.
Nagamoto-Combs K, Kulas J, Combs CK. A novel cell line from spontaneously immortalized murine microglia. J Neurosci Methods. 2014;233:187-198.
Weisel JW, Nagaswami C, Woodhead JL, DeLa Cadena RA, Page JD, Colman RW. The shape of high molecular weight kininogen. Organization into structural domains, changes with activation, and interactions with prekallikrein, as determined by electron microscopy. J Biol Chem. 1994;269:10100-10106.
Melo KR, Gutierrez A, Nascimento FD, et al. Involvement of heparan sulfate proteoglycans in cellular uptake of high molecular weight kininogen. Biol Chem. 2009;390:145-155.
Damasceno IZ, Melo KR, Nascimento FD, et al. Bradykinin release avoids high molecular weight kininogen endocytosis. PLoS One. 2015;10:e0121721.
Yang A, Dai J, Xie Z, et al. High molecular weight kininogen binds phosphatidylserine and opsonizes urokinase plasminogen activator receptor-mediated efferocytosis. J Immunol. 2014;192:4398-4408.
Lee CY, Landreth GE. The role of microglia in amyloid clearance from the AD brain. J Neural Transm (Vienna). 2010;117:949-960.