النتائج

في هذه الدراسة، تم تحليل ما مجموعه 12,048 مشاركًا مع بيانات تصوير PET للتاو عبر 42 مجموعة في جميع أنحاء العالم. شملت المجموعة 7,394 فردًا غير مصابين بضعف إدراكي (CU) (متوسط العمر: 68.7 ± 11.1 سنة، 55.9% نساء، 30.9% إيجابي Aβ)، و2,177 مصابًا بضعف إدراكي خفيف (MCI) (متوسط العمر: 71.3 ± 8.8 سنة، 45.0% نساء، 59.3% إيجابي Aβ)، و2,477 مصابًا بالخرف (متوسط العمر: 69.9 ± 9.0 سنة، 50.9% نساء، 76.8% إيجابي Aβ). بالإضافة إلى ذلك، تم تضمين 5,072 مشاركًا من ثلاث مجموعات تشريح مستقلة، تتكون من 1,026 CU، و661 MCI، و3,385 حالة خرف.

عرفت الدراسة ‘إيجابية التاو’ على أنها مسح PET للتاو غير الطبيعي بناءً على عتبة محددة للمجموعة تعادل المتوسط + 2 انحراف معياري (s.d.) في الأفراد غير المصابين بضعف إدراكي Aβ-negative الذين تتراوح أعمارهم ≥50 عامًا، مع التركيز على مناطق اهتمام مرض الزهايمر (AD) المعروفة في قشرة الفص الصدغي. استكشفت التحليلات الثانوية إيجابية PET للتاو باستخدام مناطق اهتمام بديلة (مثل قشرة 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Results

In this study, a total of 12,048 participants with tau PET imaging data were analyzed across 42 cohorts globally. The cohort included 7,394 cognitively unimpaired (CU) individuals (mean age: 68.7 ± 11.1 years, 55.9% women, 30.9% Aβ positive), 2,177 with mild cognitive impairment (MCI) (mean age: 71.3 ± 8.8 years, 45.0% women, 59.3% Aβ positive), and 2,477 with dementia (mean age: 69.9 ± 9.0 years, 50.9% women, 76.8% Aβ positive). Additionally, 5,072 participants from three independent autopsy cohorts were included, comprising 1,026 CU, 661 MCI, and 3,385 dementia cases.

The study defined ‘tau positivity’ as an abnormal tau PET scan based on a cohort-specific threshold of mean + 2 standard deviations (s.d.) in Aβ-negative CU individuals aged ≥50 years, focusing on established Alzheimer’s disease (AD) regions of interest (ROI) in the temporal cortex. Secondary analyses explored tau PET positivity using alternative ROIs (such as the entorhinal cortex) and varying thresholds (mean + 1 s.d. and mean + 1.5 s.d.), as well as different thresholding methods like Gaussian mixture modeling. The term ‘prevalence’ in this context refers to the frequency of tau PET positivity observed within the dataset.

Discussion

The study investigates the prevalence of tau pathology, as measured by positron emission tomography (PET), across various diagnostic groups, including cognitively unimpaired (CU) individuals, those with mild cognitive impairment (MCI), and dementia patients. It reveals that tau positivity in the temporal cortex is significantly influenced by age and amyloid-beta (Aβ) status. Specifically, tau positivity was found to be 7.6% in CU individuals, 36.8% in MCI, and 64.4% in dementia patients. Notably, Aβ-positive CU participants exhibited a tau positivity rate of 20.0%, compared to just 2.1% in Aβ-negative CU individuals. The findings also indicate that tau positivity increases with age, particularly among Aβ-negative individuals, while it decreases in Aβ-positive individuals with MCI and dementia as they age.

Furthermore, the study highlights the role of the APOE ε4 allele in tau pathology, showing that carriers exhibit tau positivity at a younger age compared to non-carriers. For instance, the estimated age for 10% tau positivity in the entorhinal cortex is 44.5 years for APOE ε4/ε4 carriers, compared to 77.5 years for non-carriers. Additionally, female sex was associated with a higher prevalence of both Aβ and tau positivity. Overall, the research underscores the complex interplay between age, Aβ status, and genetic factors in the development of tau pathology, providing critical insights for clinical interpretations and future studies on Alzheimer’s disease.