Mold, MJ ORCID: https://orcid.org/0000-0002-4616-6204, O’Farrell, A, Morris, B and Exley, C ORCID: https://orcid.org/0000-0002-5116-7607 (2021) Aluminum and Tau in Neurofibrillary Tangles in Familial Alzheimer’s Disease. Journal of Alzheimer's Disease Reports, 5 (1). 283 - 294.

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Abstract

Background: Familial Alzheimer’s disease (fAD) is driven by genetic predispositions affecting the expression and metabolism of the amyloid-β protein precursor. Aluminum is a non-essential yet biologically-reactive metal implicated in the etiology of AD. Recent research has identified aluminum intricately and unequivocally associated with amyloid-β in senile plaques and, more tentatively, co-deposited with neuropil-like threads in the brains of a Colombian cohort of donors with fAD.

Objective: Herein, we have assessed the co-localization of aluminum to immunolabelled phosphorylated tau to probe the potential preferential binding of aluminum to senile plaques or neurofibrillary tangles in the same Colombian kindred.

Methods: Herein, we have performed phosphorylated tau-specific immunolabelling followed by aluminum-specific fluorescence microscopy of the identical brain tissue sections via a sequential labelling method.

Results: Aluminum was co-localized with immunoreactive phosphorylated tau in the brains of donors with fAD. While aluminum was predominantly co-located to neurofibrillary tangles in the temporal cortex, aluminum was more frequently co-deposited with cortical senile plaques.

Conclusion: These data suggest that the co-deposition of aluminum with amyloid-β precedes that with neurofibrillary tangles. Extracellularly deposited amyloid-β may also be more immediately available to bind aluminum versus intracellular aggregates of tau. Therapeutic approaches to reduce tau have demonstrated the amelioration of its synergistic interactions with amyloid-β, ultimately reducing tau pathology and reducing neuronal loss. These data support the intricate associations of aluminum in the neuropathology of fAD, of which its subsequent reduction may further therapeutic benefits observed in ongoing clinical trials in vivo.

Item Type: Article
Additional Information: © 2021 – The authors. Published by IOS Press. This is an Open Access article distributed under the terms of the Creative Commons Attribution-NonCommercial License (CC BY-NC 4.0).
Uncontrolled Keywords: Aluminum in human brain tissueamy; loid-beta; familial Alzheimer's disease; neurofibrillary tangles; senile plaques; tau
Subjects: Q Science > Q Science (General)
Q Science > QD Chemistry
Q Science > QD Chemistry > QD415 Biochemistry
Divisions: Faculty of Natural Sciences > School of Chemical and Physical Sciences
Depositing User: Symplectic
Date Deposited: 16 Jun 2021 08:12
Last Modified: 14 Jul 2021 10:22
URI: https://eprints.keele.ac.uk/id/eprint/9733

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