Premium
EF hd2 is a novel amyloid protein associated with pathological tau in Alzheimer's disease
Author(s) -
FerrerAcosta Yancy,
RodríguezCruz Eva N.,
Orange François,
JesúsCortés Hector,
Madera Bismark,
VaquerAlicea Jaime,
Ballester Juan,
Guinel Maxime J.F.,
Bloom George S.,
Vega Irving E.
Publication year - 2013
Publication title -
journal of neurochemistry
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.75
H-Index - 229
eISSN - 1471-4159
pISSN - 0022-3042
DOI - 10.1111/jnc.12155
Subject(s) - pathological , neurodegeneration , microbiology and biotechnology , amyloid (mycology) , biology , chemistry , pathology , disease , medicine
EF hd2 is a conserved calcium‐binding protein, abundant within the central nervous system. Previous studies identified EF hd2 associated with pathological forms of tau proteins in the tauopathy mouse model JNPL 3, which expresses the human tau P301L mutant. This association was validated in human tauopathies, such as Alzheimer's disease ( AD ). However, the role that EF hd2 may play in tauopathies is still unknown. Here, we show that EF hd2 formed amyloid structures in vitro , a capability that is reduced by calcium ions. Electron microscopy ( EM ) analyses demonstrated that recombinant EF hd2 formed filamentous structures. EM analyses of sarkosyl‐insoluble fractions derived from human AD brains also indicated that EF hd2 co‐localizes with aggregated tau proteins and formed granular structures. Immunohistological analyses of brain slices demonstrated that EF hd2 co‐localizes with pathological tau proteins in AD brains, confirming the co‐aggregation of EF hd2 and pathological tau. Furthermore, EF hd2's coiled‐coil domain mediated its self‐oligomerization in vitro and its association with tau proteins in JNPL 3 mouse brain extracts. The results demonstrate that EF hd2 is a novel amyloid protein associated with pathological tau proteins in AD brain and that calcium binding may regulate the formation of EF hd2's amyloid structures. Hence, EF hd2 may play an important role in the pathobiology of tau‐mediated neurodegeneration.