Amyloid‐beta misfolding and GFAP predict risk of clinical Alzheimer's disease diagnosis within 17 years

Abstract

IntroductionBlood‐based biomarkers for Alzheimer's disease (AD) are urgently needed. Here, four plasma biomarkers were measured at baseline in a community‐based cohort followed over 17 years, and the association with clinical AD risk was determined.MethodsAmyloid beta (Aβ) misfolding status as a structure‐based biomarker as well as phosphorylated tau 181 (P‐tau181), glial fibrillary acidic protein (GFAP), and neurofilament light (NfL) concentration levels were determined at baseline in heparin plasma from 68 participants who were diagnosed with AD and 240 controls without dementia diagnosis throughout follow‐up.ResultsAβ misfolding exhibited high disease prediction accuracy of AD diagnosis within 17 years. Among the concentration markers, GFAP showed the best performance, followed by NfL and P‐tau181. The combination of Aβ misfolding and GFAP increased the accuracy.DiscussionAβ misfolding and GFAP showed a strong ability to predict clinical AD risk and may be important early AD risk markers. Aβ misfolding illustrated its potential as a prescreening tool for AD risk stratification in older adults.

Serum NfL and GFAP are associated with incident dementia and dementia mortality in older adults: The cardiovascular health study

“…Second, we address the role of the durability of biomarker measurements to cognitive outcomes. Although previous prospective investigations of NfL, GFAP, and t-tau in relation to dementia-specific outcomes have spanned up to 17 years, 6 only one study has, to our knowledge, TA B L E 2 Association of serum N4PA protein levels with incident dementia and dementia-specific mortality risk. specifically addressed the role of event proximity.…”

“…In the longest previous study to date, Beyer et al. found that baseline plasma GFAP, but not NfL, was associated with a higher odds of AD within 17 years ( N = 308, including 68 cases, mean age of 67 years) 6 . Verberk et al 5 .…”

Translating blood biomarkers into clinical practice for Alzheimer's disease: Challenges and perspectives

“…Using the immuno‐infrared sensor assay, they found that a shift in the distribution of the secondary structure of Aβ to the β‐sheet structure supported AD diagnosis with good performance 57 . In their recent study in a community‐based prospective cohort, Aβ misfolding exhibited higher prediction accuracy of clinical AD diagnosis within 17 years than absolute concentrations of p‐tau181, NfL, and GFAP 58 . Additionally, Aβ42 was found to be decreased by some immunoassays or mass spectrum assays but increased by some other methods, such as the real‑time quaking‐induced conversion (RT‐QuIC) assay, in the CSF or blood of AD patients, 59 suggesting that these methods measure different things.…”

“…57 In their recent study in a community-based prospective cohort, Aβ misfolding exhibited higher prediction accuracy of clinical AD diagnosis within 17 years than absolute concentrations of p-tau181, NfL, and GFAP. 58 Additionally, Aβ42 was found to be decreased by some immunoassays or mass spectrum assays but increased by some other methods, such as the real-time quaking-induced conversion (RT-QuIC) assay, in the CSF or blood of AD patients, 59 suggesting that these methods measure This may guide us to find suitable blood biomarkers for AD.…”

Early Diagnosis of Alzheimer’s Disease: Moving Toward a Blood-Based Biomarkers Era

“…30,31 Furthermore, plasma GFAP levels were significantly elevated in Aβ+ CU participants compared to Aβ-CU participants, 32 and it could predict clinical AD risk. 33 In addition, one study with small sample scale reported that serum GFAP could discriminate AD from FTLD patients (with 89% sensitivity and a specificity of 79%). 30 However, in another study, higher serum GFAP level is also found in FTLD and can serve as a disease severity biomarker for FTLD.…”