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Background <p>Plasma phosphorylated tau (p-tau) biomarkers have improved the diagnosis of Alzheimer’s disease (AD), but evidence in early-onset populations remains limited. We evaluated the diagnostic performance of plasma p-tau217 and p-tau181 levels in patients with early-onset AD (EOAD) and early-onset frontotemporal dementia (EOFTD).</p> Methods <p>We analyzed 185 patients (EOAD = 150, EOFTD = 35) aged ≤ 65&#xa0;years from the LEAF study (2021–2023). Plasma p-tau217, p-tau181, neurofilament light (NfL), and glial fibrillary acidic protein (GFAP) levels were measured by immunoassays.</p> Results <p>Both plasma p-tau217 (AUC = 0.831) and p-tau181 (AUC = 0.862) levels demonstrated high discriminative performance, with no significant difference between the two p-tau isoforms. P-tau levels were higher in patients with EOAD, whereas NfL levels were higher in EOFTD and were elevated in those with EOAD participants with severe hippocampal atrophy. Adding NfL, GFAP, and <i>APOE</i> ε4 status further improved the discriminative accuracy for differentiating EOAD from EOFTD.</p> Conclusions <p>Plasma p-tau217 and p-tau181 are effective biomarkers for distinguishing biologically defined EOAD from EOFTD. Incorporating NfL, GFAP, and <i>APOE</i> ε4 status further enhances diagnostic accuracy.</p>

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Blood-based multimodal biomarker models for differentiating early-onset Alzheimer’s disease from frontotemporal dementia: a longitudinal study of early-onset dementia and family members (LEAF) study

  • 期刊论文

  • 发表日期：

    2026年7月20日

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  • Hyuk Sung Kwon,
  • So Young Moon,
  • Mina Hwang,
  • Hee Jin Kim,
  • Sun Min Lee,
  • Na-Yeon Jung,
  • Hyemin Jang,
  • Jeong-Min Baek,
  • Min-Ju Kim,
  • Myung-Hoon Han,
  • Henrik Zetterberg,
  • Kaj Blennow,
  • Liana G. Apostolova,
  • Seong-Ho Koh,
  • Eun-Joo Kim

摘要

Background

Plasma phosphorylated tau (p-tau) biomarkers have improved the diagnosis of Alzheimer’s disease (AD), but evidence in early-onset populations remains limited. We evaluated the diagnostic performance of plasma p-tau217 and p-tau181 levels in patients with early-onset AD (EOAD) and early-onset frontotemporal dementia (EOFTD).

Methods

We analyzed 185 patients (EOAD = 150, EOFTD = 35) aged ≤ 65 years from the LEAF study (2021–2023). Plasma p-tau217, p-tau181, neurofilament light (NfL), and glial fibrillary acidic protein (GFAP) levels were measured by immunoassays.

Results

Both plasma p-tau217 (AUC = 0.831) and p-tau181 (AUC = 0.862) levels demonstrated high discriminative performance, with no significant difference between the two p-tau isoforms. P-tau levels were higher in patients with EOAD, whereas NfL levels were higher in EOFTD and were elevated in those with EOAD participants with severe hippocampal atrophy. Adding NfL, GFAP, and APOE ε4 status further improved the discriminative accuracy for differentiating EOAD from EOFTD.

Conclusions

Plasma p-tau217 and p-tau181 are effective biomarkers for distinguishing biologically defined EOAD from EOFTD. Incorporating NfL, GFAP, and APOE ε4 status further enhances diagnostic accuracy.