Three-Dimensional Tomographic Imaging and Characterization of Iron Compounds within Alzheimer's Plaque Core Material

Abstract

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.

Biometals and Their Therapeutic Implications in Alzheimer's Disease

“…Iron elevation in AD brains, first demonstrated in 1953 [99], is a consistently reported finding [99][100][101][102][103][104][105][106][107][108]. Neuronal iron deposition causes oxidative stress via the Fenton reaction, which might contribute to elevated oxidative stress observed in the AD brain [109].…”

Demonstration of aluminum in amyloid fibers in the cores of senile plaques in the brains of patients with Alzheimer’s disease

“…On the other hand, Beauchemin and Kisilevsky detected Al in isolated senile plaques cores from the AD brain using inductively coupled plasma mass spectrometry [23]. Recently, Collingwood et al isolated fragments of senile plaque cores (approximately 1-2 lm in diameter, round or oval in shape) from frozen cortical brain tissues of AD patients and demonstrated Al in half of these isolated plaque core fragments by EDX combined with transmission electron microscopy (TEM-EDX) analysis [24]. In contrast, Walton detected no Al in the cores of senile plaques using a novel histochemical method that clearly stained Al in the nuclei of nerve cells and neurofibrillary tangles in the AD brain [10].…”

Alzheimer's Disease: What is the Connection between Amyloid Plaques, Magnetite and Memory?

“…Magnetite is present in the brain [3] and biogenic magnetite is associated with neurogenerative diseases like AD and Parkinson. It has been shown that the amount of magnetite present is generally high in AD brain [4][5][6]. In plaque core material magnetite has been detected as the dominant iron compound [6,7].…”