Three-dimensional tomographic imaging and characterization of iron compounds within Alzheimer's plaque core material.
Although it has been known for over 50 years that abnormal concentrations of iron are associated with virtually all neurodegenerative diseases, including Alzheimer's disease, its origin, nature and role have remained a mystery. Here, we use high-resolution transmission electron microscopy (HR-TEM), energy dispersive X-ray (EDX) spectroscopy and electron energy-loss spectroscopy (EELS), electron tomography, and electron diffraction to image and characterize iron-rich plaque core material - a hallmark of Alzheimer's disease pathology - in three dimensions. In these cores, we unequivocally identify biogenic magnetite and/or maghemite as the dominant iron compound. Our results provide an indication that abnormal iron biomineralization processes are likely occurring within the plaque or the surrounding diseased tissue and may play a role in aberrant peptide aggregation. The size distribution of the magnetite cores implies formation from a ferritin precursor, implicating a malfunction of the primary iron storage protein in the brain.
Collingwood
Joanna F
JF
Institute of Science and Technology in Medicine, Keele University, Thornburrow Drive, Hartshill, Stoke-on-Trent, UK.
Chong
Ryan K K
RK
Kasama
Takeshi
T
Cervera-Gontard
Lionel
L
Dunin-Borkowski
Rafal E
RE
Perry
George
G
Pósfai
Mihály
M
Siedlak
Sandra L
SL
Simpson
Edward T
ET
Smith
Mark A
MA
Dobson
Jon
J
D000368:Aged; D000369:Aged, 80 and over; D000544:Alzheimer Disease / Q000473:pathology*; D002540:Cerebral Cortex / Q000473:pathology*; D004577:Electron Probe Microanalysis; D052203:Ferrosoferric Oxide / Q000032:analysis; D006801:Humans; D007091:Image Processing, Computer-Assisted; D021621:Imaging, Three-Dimensional; D058085:Iron Compounds / Q000032:analysis*; D008854:Microscopy, Electron; D058225:Plaque, Amyloid / Q000473:pathology*
D058085:Iron Compounds; D052203:Ferrosoferric Oxide