Microscopy assessment of a fluorescence [18F] flortaucipir analog (T726) shows neuropathological overlap with 3R and 4R tau lesions

IF 11.1 1区医学 Q1 CLINICAL NEUROLOGY Alzheimer's & Dementia Pub Date : 2024-10-22 DOI:10.1002/alz.14330

Rodolfo G. Gatto, Youssef Hossam, R. Ross Reichard, Val J. Lowe, Jennifer L. Whitwell, Keith A. Josephs

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Abstract

BACKGROUND

[¹⁸F] flortaucipir (FTP) binding to paired helical filament (PHF) tau in Alzheimer's disease (AD) is well accepted. Binding to 3R and 4R tau in frontotemporal lobar degeneration (FTLD) is controversial. We aimed to investigate whether an FTP fluorescent analog (T726) can help shed light on this controversy.

METHOD

We assessed T726 binding to amyloid beta (Aβ) and different tau isoforms in nine subjects (one control, three with Alzheimer's disease [AD], and five with FTLD) with different 3R and 4R tauopathies using fluorescence confocal microscopy.

RESULTS

T726 did not colocalize with Aβ but showed significant co-localization with PHF tau in AD. We also observed some, albeit limited, co-localization of T726 with 3R and 4R tau lesions in FTLD.

DISCUSSION

This study's findings support FTP binding to some 3R and 4R tau lesions in FTLD. Further studies are needed to understand the biology of why FTP binds some but not all FTLD tau lesions.

Highlights

Flortaucipir analog (T726) showed significant co-localization with paired helical filament (PHF) tau in Alzheimer's disease (AD).
Colocalization between T726 with 3R and 4R tau lesions was observed in frontotemporal lobar degeneration (FTLD).
Not all 4R tau lesions bind to T726 across different FTLD brain regions.

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荧光[18F]氟陶西哌类似物（T726）的显微镜评估显示神经病理学与3R和4R tau病变重叠

[18F]氟曲霉素（FTP）与阿尔茨海默病（AD）中成对螺旋丝（PHF）tau的结合已被广泛接受。在额颞叶变性（FTLD）中，与3R和4R tau的结合还存在争议。我们旨在研究一种FTP荧光类似物（T726）是否有助于揭示这一争议。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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来源期刊

Alzheimer's & Dementia 医学-临床神经学

CiteScore

14.50

自引率

5.00%

发文量

299

审稿时长

3 months

期刊介绍： Alzheimer's & Dementia is a peer-reviewed journal that aims to bridge knowledge gaps in dementia research by covering the entire spectrum, from basic science to clinical trials to social and behavioral investigations. It provides a platform for rapid communication of new findings and ideas, optimal translation of research into practical applications, increasing knowledge across diverse disciplines for early detection, diagnosis, and intervention, and identifying promising new research directions. In July 2008, Alzheimer's & Dementia was accepted for indexing by MEDLINE, recognizing its scientific merit and contribution to Alzheimer's research.