Scholarlink

Background <p>Amyloid-β and tau deposition follow distinct spatial and temporal trajectories across the Alzheimer’s disease (AD) continuum. Amyloid accumulation occurs early in the disease course, whereas tau pathology is more closely associated with neurodegeneration and clinical progression. Characterizing stage-specific regional divergence between amyloid and tau deposition may refine biomarker-based disease staging and improve prognostic assessment.</p> Methods <p>We analyzed participants from the BATON study who underwent amyloid PET with <sup>18</sup>F-flutemetamol, tau PET with <sup>18</sup>F-MK-6240, and 3D MRI within a three-month interval. Participants were classified into cognitively normal amyloid-negative controls (CNA, <i>n</i> = 101) and the AD continuum (<i>n</i> = 102), comprising preclinical AD (PCA, <i>n</i> = 47), mild cognitive impairment due to AD (MCA, <i>n</i> = 24), and AD dementia (ADD, <i>n</i> = 31). Standardized uptake value ratios (SUVRs) were calculated using the Centiloid and CenTauR frameworks, and voxel-wise tau-to-amyloid ratio (TAR) images were generated. Voxel-wise and region-of-interest analyses were performed to compare regional patterns of amyloid deposition, tau accumulation, and TAR across disease stages.</p> Results <p>Amyloid deposition was already widespread at the PCA stage, involving the frontal, posterior cingulate/precuneus, and temporal cortices. In contrast, tau deposition in PCA was largely confined to the medial temporal lobe. With progression to MCA and ADD, tau burden increased substantially and extended to the lateral temporal, parietal, and frontal cortices. TAR analysis demonstrated high values in the medial temporal cortex at the PCA stage, followed by decreasing TAR in frontal regions during MCA and a tau-dominant neocortical pattern in ADD.</p> Conclusions <p>Amyloid and tau exhibit distinct and stage-dependent regional dissociation across the AD continuum. TAR imaging effectively captures this divergence, reflecting early medial temporal tau predominance and subsequent neocortical tau expansion. These findings support the utility of integrated amyloid–tau PET metrics for refined disease staging and longitudinal therapeutic monitoring.</p>

错误：搜索内容不能为空，请输入英文关键词
错误：关键词超出字数限制，请精简
高级检索

Stage-specific regional distribution of amyloid and tau deposition across the Alzheimer’s disease continuum revealed by tau-to-amyloid ratio imaging

  • 期刊论文

  • 出版模式：

    开放获取

  • 发表日期：

    2026年5月29日

查看全文
  • Kazunari Ishii,
  • Takahiro Yamada,
  • Kohei Hanaoka,
  • Yasuyuki Kojita,
  • Atsushi Kono,
  • Hayato Kaida,
  • Takashi Nihashi,
  • Keita Sakurai,
  • Takashi Kato,
  • Akinori Nakamura

摘要

Background

Amyloid-β and tau deposition follow distinct spatial and temporal trajectories across the Alzheimer’s disease (AD) continuum. Amyloid accumulation occurs early in the disease course, whereas tau pathology is more closely associated with neurodegeneration and clinical progression. Characterizing stage-specific regional divergence between amyloid and tau deposition may refine biomarker-based disease staging and improve prognostic assessment.

Methods

We analyzed participants from the BATON study who underwent amyloid PET with 18F-flutemetamol, tau PET with 18F-MK-6240, and 3D MRI within a three-month interval. Participants were classified into cognitively normal amyloid-negative controls (CNA, n = 101) and the AD continuum (n = 102), comprising preclinical AD (PCA, n = 47), mild cognitive impairment due to AD (MCA, n = 24), and AD dementia (ADD, n = 31). Standardized uptake value ratios (SUVRs) were calculated using the Centiloid and CenTauR frameworks, and voxel-wise tau-to-amyloid ratio (TAR) images were generated. Voxel-wise and region-of-interest analyses were performed to compare regional patterns of amyloid deposition, tau accumulation, and TAR across disease stages.

Results

Amyloid deposition was already widespread at the PCA stage, involving the frontal, posterior cingulate/precuneus, and temporal cortices. In contrast, tau deposition in PCA was largely confined to the medial temporal lobe. With progression to MCA and ADD, tau burden increased substantially and extended to the lateral temporal, parietal, and frontal cortices. TAR analysis demonstrated high values in the medial temporal cortex at the PCA stage, followed by decreasing TAR in frontal regions during MCA and a tau-dominant neocortical pattern in ADD.

Conclusions

Amyloid and tau exhibit distinct and stage-dependent regional dissociation across the AD continuum. TAR imaging effectively captures this divergence, reflecting early medial temporal tau predominance and subsequent neocortical tau expansion. These findings support the utility of integrated amyloid–tau PET metrics for refined disease staging and longitudinal therapeutic monitoring.