{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,21]],"date-time":"2026-08-21T11:49:41Z","timestamp":1787312981496,"version":"build-2736575974"},"reference-count":56,"publisher":"SAGE Publications","issue":"1","license":[{"start":{"date-parts":[[2020,10,27]],"date-time":"2020-10-27T00:00:00Z","timestamp":1603756800000},"content-version":"unspecified","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by-nc\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["JAD"],"published-print":{"date-parts":[[2020,10,27]]},"abstract":"<jats:p>Background: Protein misfolding disorders are frequently implicated in neurodegenerative conditions. Familial Alzheimer\u2019s disease (fAD) is an early-onset and aggressive form of Alzheimer\u2019s 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\u2019s 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-\u03b2 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\u2019s 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\u2019s disease.<\/jats:p>","DOI":"10.3233\/jad-200838","type":"journal-article","created":{"date-parts":[[2020,9,8]],"date-time":"2020-09-08T11:03:52Z","timestamp":1599563032000},"page":"139-149","source":"Crossref","is-referenced-by-count":31,"title":["Aluminum and Neurofibrillary Tangle Co-Localization in Familial Alzheimer\u2019s Disease and Related Neurological Disorders"],"prefix":"10.1177","volume":"78","author":[{"given":"Matthew John","family":"Mold","sequence":"first","affiliation":[{"name":"The Birchall Centre, Lennard-Jones Laboratories, Keele University, Keele, Staffordshire, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Adam","family":"O\u2019Farrell","sequence":"additional","affiliation":[{"name":"School of Life Sciences, Huxley Building, Keele University, Keele, 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