Aluminum and Tau in Neurofibrillary Tangles in Familial Alzheimer’s Disease

Abstract

Background: Familial Alzheimer’s disease (fAD) is driven by genetic predispositions affecting the expression and metabolism of the amyloid-ß 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-ß 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-ß precedes that with neurofibrillary tangles. Extracellularly deposited amyloid-ß 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-ß, 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.

Citation

(2021). Aluminum and Tau in Neurofibrillary Tangles in Familial Alzheimer’s Disease. Journal of Alzheimer's Disease Reports, 283 - 294. https://doi.org/10.3233/ADR-210011

• Acceptance Date: Mar 11, 2021
• Publication Date: Mar 9, 2021
• Journal: Journal of Alzheimer's Disease Reports
• Print ISSN: 2542-4823
• Publisher: IOS Press
• Pages: 283 - 294
• DOI: https://doi.org/10.3233/ADR-210011
• Keywords: Aluminum in human brain tissueamy; loid-beta; familial Alzheimer's disease; neurofibrillary tangles; senile plaques; tau
• Publisher URL: https://content.iospress.com/articles/journal-of-alzheimers-disease-reports/adr210011