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However, the distribution of TTR and its affinity to A\u03b2 in both healthy human brains and those of AD patients remain unclear. We therefore examined TTR in human brains using postmortem brain samples. Paraffin sections and extracted protein samples were prepared from AD and control (non\u2010AD) brains. Immunohistochemistry was performed to detect TTR expression patterns, and immunofluorescent staining was used to reveal the relationships between the intracellular and extracellular localizations of TTR and A\u03b2. We also performed western blotting for TTR using brain extracts. In immunohistochemical staining of the human brain, TTR signal was detected not only in extracellular tissue but also in the cytoplasm of neurons and glia. The TTR\u2010positive area was significantly greater in AD brains than in non\u2010AD brains. However, expression of <jats:italic>TTR<\/jats:italic> transcripts did not differ between AD and non\u2010AD brains in our previously obtained RNA\u2010sequencing and microarray data. Immunofluorescent staining with multiple antibodies revealed that TTR was co\u2010localized with A\u03b2 in the cytoplasm of neurons. In extracellular A\u03b2 plaques, TTR presented in the same region but was not co\u2010localized with dense A\u03b2 fibrils. Together, our results indicate that TTR is widely expressed in the human brain rather than being limited to the choroid plexus and that TTR is more abundant in AD brains. Our results also suggest that the affinity between TTR and A\u03b2 changes depending on the structure of A\u03b2. Our data will be valuable for the future development of TTR\u2010related AD preventative methods and medications.<\/jats:p>","DOI":"10.1111\/neup.70015","type":"journal-article","created":{"date-parts":[[2025,5,31]],"date-time":"2025-05-31T06:29:57Z","timestamp":1748672997000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":3,"title":["Intracellular and Extracellular Localization of Transthyretin and Its Association With Amyloid\u2010\u03b2 in\u00a0Alzheimer's Disease Brains"],"prefix":"10.1111","volume":"45","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-0167-0391","authenticated-orcid":false,"given":"Yuri","family":"Mizuno","sequence":"first","affiliation":[{"name":"Department of Neurology, Neurological Institute, Graduate School of Medical Sciences Kyushu University  Fukuoka Japan"},{"name":"Department of Neurology, School of Medicine International University of Health and Welfare  Narita Japan"},{"name":"Neuropathology 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