EFhd2 is a novel amyloid protein associated with pathological tau in Alzheimer's disease.
Submitted by Héctor J De Jesús-Cortés on
Title | EFhd2 is a novel amyloid protein associated with pathological tau in Alzheimer's disease. |
Publication Type | Journal Article |
Year of Publication | 2013 |
Authors | Ferrer-Acosta, Y, Rodríguez-Cruz, EN, Orange, F, De Jesús-Cortés, H, Madera, B, Vaquer-Alicea, J, Ballester, J, Guinel, MJ-F, Bloom, GS, Vega, IE |
Journal | J Neurochem |
Volume | 125 |
Issue | 6 |
Pagination | 921-31 |
Date Published | 2013 Jun |
ISSN | 1471-4159 |
Keywords | Alzheimer Disease, Amyloid, Amyloidogenic Proteins, Animals, Brain, Calcium-Binding Proteins, Humans, Mice, Mice, Transgenic, Neurofibrillary Tangles, Protein Multimerization, Protein Structure, Tertiary, tau Proteins |
Abstract | EFhd2 is a conserved calcium-binding protein, abundant within the central nervous system. Previous studies identified EFhd2 associated with pathological forms of tau proteins in the tauopathy mouse model JNPL3, which expresses the human tau(P301L) mutant. This association was validated in human tauopathies, such as Alzheimer's disease (AD). However, the role that EFhd2 may play in tauopathies is still unknown. Here, we show that EFhd2 formed amyloid structures in vitro, a capability that is reduced by calcium ions. Electron microscopy (EM) analyses demonstrated that recombinant EFhd2 formed filamentous structures. EM analyses of sarkosyl-insoluble fractions derived from human AD brains also indicated that EFhd2 co-localizes with aggregated tau proteins and formed granular structures. Immunohistological analyses of brain slices demonstrated that EFhd2 co-localizes with pathological tau proteins in AD brains, confirming the co-aggregation of EFhd2 and pathological tau. Furthermore, EFhd2's coiled-coil domain mediated its self-oligomerization in vitro and its association with tau proteins in JNPL3 mouse brain extracts. The results demonstrate that EFhd2 is a novel amyloid protein associated with pathological tau proteins in AD brain and that calcium binding may regulate the formation of EFhd2's amyloid structures. Hence, EFhd2 may play an important role in the pathobiology of tau-mediated neurodegeneration. |
DOI | 10.1111/jnc.12155 |
Alternate Journal | J. Neurochem. |
PubMed ID | 23331044 |
PubMed Central ID | PMC3676478 |
Grant List | 1SC1NS066988 / NS / NINDS NIH HHS / United States 5R25GM061151 / GM / NIGMS NIH HHS / United States 8R25NS080687 / NS / NINDS NIH HHS / United States R25 GM061151 / GM / NIGMS NIH HHS / United States R25 NS080687 / NS / NINDS NIH HHS / United States SC1 NS066988 / NS / NINDS NIH HHS / United States T34 GM007821 / GM / NIGMS NIH HHS / United States |