Aluminium co-localises with Biondi ring tangles in Parkinson's disease and epilepsy.

Aluminium is known to accumulate in neuropathological hallmarks. However, such has only tentatively been suggested in Biondi ring tangles. Owing to their intracellular and filamentous structure rich in ß-pleated sheets, Biondi ring tangles might attract the adventitious binding of aluminium in regions of the blood-cerebrospinal fluid barrier. The study's objective was to establish whether aluminium co-localises with Biondi ring tangles in the brains of Parkinson's disease donors versus a donor that went on to develop late-onset epilepsy. Herein, we have performed immunohistochemistry for phosphorylated tau, complemented with aluminium-specific fluorescence microscopy in the choroid plexus of Parkinson's disease donors and in a donor that developed late-onset epilepsy. Aluminium co-localises with lipid-rich Biondi ring tangles in the choroid plexus. While Biondi ring tangles are not composed of phosphorylated tau, the latter is identified in nuclei of choroidal cells where aluminium and Biondi ring tangles are co-located. Although Biondi ring tangles are considered artefacts in imaging studies using positron emission tomography, their ability to bind aluminium and then release it upon their subsequent rupture and escape from choroidal cells may allow for a mechanism that may propagate for aluminium toxicity in vivo.

Aluminum and Tau in Neurofibrillary Tangles in Familial Alzheimer's Disease.

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.

Aluminum and Neurofibrillary Tangle Co-Localization in Familial Alzheimer's Disease and Related Neurological Disorders.

BACKGROUND: Protein misfolding disorders are frequently implicated in neurodegenerative conditions. Familial Alzheimer's disease (fAD) is an early-onset and aggressive form of Alzheimer's disease (AD), driven through autosomal dominant mutations in genes encoding the amyloid precursor protein and presenilins 1 and 2. The incidence of epilepsy is higher in AD patients with shared neuropathological hallmarks in both disease states, including the formation of neurofibrillary tangles. Similarly, in Parkinson's disease, dementia onset is known to follow neurofibrillary tangle deposition. OBJECTIVE: Human exposure to aluminum has been linked to the etiology of neurodegenerative conditions and recent studies have demonstrated a high level of co-localization between amyloid-ß and aluminum in fAD. In contrast, in a donor exposed to high levels of aluminum later developing late-onset epilepsy, aluminum and neurofibrillary tangles were found to deposit independently. Herein, we sought to identify aluminum and neurofibrillary tangles in fAD, Parkinson's disease, and epilepsy donors. METHODS: Aluminum-specific fluorescence microscopy was used to identify aluminum in neurofibrillary tangles in human brain tissue. RESULTS: We observed aluminum and neurofibrillary-like tangles in identical cells in all respective disease states. Co-deposition varied across brain regions, with aluminum and neurofibrillary tangles depositing in different cellular locations of the same cell. CONCLUSION: Neurofibrillary tangle deposition closely follows cognitive-decline, and in epilepsy, tau phosphorylation associates with increased mossy fiber sprouting and seizure onset. Therefore, the presence of aluminum in these cells may exacerbate the accumulation and misfolding of amyloidogenic proteins including hyperphosphorylated tau in fAD, epilepsy, and Parkinson's disease.