{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,5]],"date-time":"2026-06-05T22:49:58Z","timestamp":1780699798475,"version":"3.54.1"},"reference-count":81,"publisher":"SAGE Publications","issue":"3","license":[{"start":{"date-parts":[[2023,5,30]],"date-time":"2023-05-30T00:00:00Z","timestamp":1685404800000},"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":[[2023,5,30]]},"abstract":"<jats:p>Background: The tau protein phosphorylated at Thr181 (p-tau181) in cerebrospinal fluid and blood is a sensitive biomarker for Alzheimer\u2019s disease (AD). Increased p-tau181 levels correlate well with amyloid-\u03b2 (A\u03b2) pathology and precede neurofibrillary tangle formation in the early stage of AD; however, the relationship between p-tau181 and A\u03b2-mediated pathology is less well understood. We recently reported that p-tau181 represents axonal abnormalities in mice with A\u03b2 pathology (AppNLGF). However, from which neuronal subtype(s) these p-tau181-positive axons originate remains elusive. Objective: The main purpose of this study is to differentiate neuronal subtype(s) and elucidate damage associated with p-tau181-positive axons by immunohistochemical analysis of AppNLGF mice brains. Methods: Colocalization between p-tau181 and (1) unmyelinated axons positive for vesicular acetylcholine transporter or norepinephrine transporter and (2) myelinated axons positive for vesicular glutamate transporter, vesicular GABA transporter, or parvalbumin in the brains of 24-month-old AppNLGF and control mice without A\u03b2 pathology were analyzed. The density of these axons was also compared. Results: Unmyelinated axons of cholinergic or noradrenergic neurons did not overlap with p-tau181. By contrast, p-tau181 signals colocalized with myelinated axons of parvalbumin-positive GABAergic interneurons but not of glutamatergic neurons. Interestingly, the density of unmyelinated axons was significantly decreased in AppNLGF mice, whereas that of glutamatergic, GABAergic, or p-tau181-positive axons was less affected. Instead, myelin sheaths surrounding p-tau181-positive axons were significantly reduced in AppNLGF mice. Conclusion: This study demonstrates that p-tau181 signals colocalize with axons of parvalbumin-positive GABAergic interneurons with disrupted myelin sheaths in the brains of a mouse model of A\u03b2 pathology.<\/jats:p>","DOI":"10.3233\/jad-230121","type":"journal-article","created":{"date-parts":[[2023,5,16]],"date-time":"2023-05-16T11:24:28Z","timestamp":1684236268000},"page":"1065-1081","source":"Crossref","is-referenced-by-count":9,"title":["Alzheimer\u2019s Disease-Related Phospho-Tau181 Signals Are Localized to\u00a0Demyelinated Axons of Parvalbumin-Positive GABAergic Interneurons in an App Knock-In Mouse Model of Amyloid-\u03b2 Pathology"],"prefix":"10.1177","volume":"93","author":[{"given":"Yu","family":"Hirota","sequence":"first","affiliation":[{"name":"Department of Neurogenetics, Center for Development of Advanced Medicine for Dementia, National Center for Geriatrics and Gerontology, Obu, Aichi, Japan"},{"name":"Japan Society for the Promotion of Science, Chiyoda-ku, Tokyo, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yasufumi","family":"Sakakibara","sequence":"additional","affiliation":[{"name":"Department of Neurogenetics, Center for Development of Advanced Medicine for Dementia, National Center for Geriatrics and Gerontology, Obu, Aichi, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kimi","family":"Takei","sequence":"additional","affiliation":[{"name":"Department of Neurogenetics, Center for Development of Advanced Medicine for Dementia, National Center for Geriatrics and Gerontology, Obu, Aichi, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Risa","family":"Nishijima","sequence":"additional","affiliation":[{"name":"Department of Neurogenetics, Center for Development of Advanced Medicine for Dementia, National Center for Geriatrics and Gerontology, Obu, Aichi, 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