Aluminum-induced amyloidogenesis and impairment in the clearance of amyloid peptides from the central nervous system in Alzheimer's disease

Yuhai Zhao¹, James M Hill², Surjyadipta Bhattacharjee³, Maire E Percy⁴, Aileen I D Pogue⁵, Walter J Lukiw⁶

Affiliations

¹ LSU Neuroscience Center, Louisiana State University Health Sciences Center, Louisiana State University , New Orleans, LA , USA ; Department of Ophthalmology, Louisiana State University Health Sciences Center, Louisiana State University , New Orleans, LA , USA.
² LSU Neuroscience Center, Louisiana State University Health Sciences Center, Louisiana State University , New Orleans, LA , USA ; Department of Ophthalmology, Louisiana State University Health Sciences Center, Louisiana State University , New Orleans, LA , USA ; Department of Microbiology, Louisiana State University Health Sciences Center, Louisiana State University , New Orleans, LA , USA.
³ LSU Neuroscience Center, Louisiana State University Health Sciences Center, Louisiana State University , New Orleans, LA , USA.
⁴ Department of Physiology, University of Toronto , Toronto, ON , Canada ; Department of Obstetrics and Gynaecology, University of Toronto , Toronto, ON , Canada ; Neurogenetics Laboratory, Surrey Place Centre , Toronto, ON , Canada.
⁵ Alchem Biotech , Toronto, ON , Canada.
⁶ LSU Neuroscience Center, Louisiana State University Health Sciences Center, Louisiana State University , New Orleans, LA , USA ; Department of Ophthalmology, Louisiana State University Health Sciences Center, Louisiana State University , New Orleans, LA , USA ; Alchem Biotech , Toronto, ON , Canada ; Department of Neurology, Louisiana State University Health Sciences Center , New Orleans, LA , USA.

PMID: 25250012
PMCID: PMC4155793
DOI: 10.3389/fneur.2014.00167

Review

Aluminum-induced amyloidogenesis and impairment in the clearance of amyloid peptides from the central nervous system in Alzheimer's disease

Yuhai Zhao et al. Front Neurol. 2014.

. 2014 Sep 5:5:167.

doi: 10.3389/fneur.2014.00167. eCollection 2014.

Authors

Yuhai Zhao¹, James M Hill², Surjyadipta Bhattacharjee³, Maire E Percy⁴, Aileen I D Pogue⁵, Walter J Lukiw⁶

Affiliations

¹ LSU Neuroscience Center, Louisiana State University Health Sciences Center, Louisiana State University , New Orleans, LA , USA ; Department of Ophthalmology, Louisiana State University Health Sciences Center, Louisiana State University , New Orleans, LA , USA.
² LSU Neuroscience Center, Louisiana State University Health Sciences Center, Louisiana State University , New Orleans, LA , USA ; Department of Ophthalmology, Louisiana State University Health Sciences Center, Louisiana State University , New Orleans, LA , USA ; Department of Microbiology, Louisiana State University Health Sciences Center, Louisiana State University , New Orleans, LA , USA.
³ LSU Neuroscience Center, Louisiana State University Health Sciences Center, Louisiana State University , New Orleans, LA , USA.
⁴ Department of Physiology, University of Toronto , Toronto, ON , Canada ; Department of Obstetrics and Gynaecology, University of Toronto , Toronto, ON , Canada ; Neurogenetics Laboratory, Surrey Place Centre , Toronto, ON , Canada.
⁵ Alchem Biotech , Toronto, ON , Canada.
⁶ LSU Neuroscience Center, Louisiana State University Health Sciences Center, Louisiana State University , New Orleans, LA , USA ; Department of Ophthalmology, Louisiana State University Health Sciences Center, Louisiana State University , New Orleans, LA , USA ; Alchem Biotech , Toronto, ON , Canada ; Department of Neurology, Louisiana State University Health Sciences Center , New Orleans, LA , USA.

PMID: 25250012
PMCID: PMC4155793
DOI: 10.3389/fneur.2014.00167

No abstract available

Keywords: Alzheimer’s disease; Aβ42 peptide monomers; TREM2; aluminum; amyloidogenesis; phagocytosis.

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Figures

**Figure 1**
**Multiple neurotoxic actions of aluminum results in an impairment in the clearance of Aβ42 peptides that drives amyloidogenesis and AD-type change**; in intra-cellular and intra-nuclear compartments, aluminum induces NF-kB (5, 14, 15), up-regulates miRNA-34a (9, 10), and down-regulates TREM2, a key microglial intra-membrane phagocytic sensor protein (–8, 11); lack of sufficient TREM2 impairs microglial cell-mediated phagocytosis and clearance of Aβ42 peptide monomers; deficits in TREM2 (but not the TREM2-associated TYROBP/DAP12 adaptor protein required for phagocytosis and Aβ42 peptide engulfment) have been widely reported in AD brain and in stressed microglial cells (7, 8, 11); in the extracellular space (upper left) aluminum aggregates Aβ42 peptide monomers into dense insoluble spherical clumps and promotes senile plaque formation; the movement of Al3+ across the plasma membrane is not well understood but may involve both active and passive transport; while microglia are able to phagocytose Aβ42 peptide monomers that they may have difficulty with higher order aggregates resulting in microglial activation and a pathogenic pro-inflammatory response that contributes to AD neuropathology.

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Aluminum-induced amyloidogenesis and impairment in the clearance of amyloid peptides from the central nervous system in Alzheimer's disease

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Aluminum-induced amyloidogenesis and impairment in the clearance of amyloid peptides from the central nervous system in Alzheimer's disease

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