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.
Institute of Science and Technology in Medicine, Keele University, Thornburrow Drive, Hartshill, Stoke-on-Trent, UK.
Joanna F
JF
Collingwood
Ryan K K
RK
Chong
Takeshi
T
Kasama
Lionel
L
Cervera-Gontard
Rafal E
RE
Dunin-Borkowski
George
G
Perry
Mihály
M
Pósfai
Sandra L
SL
Siedlak
Edward T
ET
Simpson
Mark A
MA
Smith
Jon
J
Dobson
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