Update on Biomarkers For Amyloid Pathology in Alzheimer’s Disease

Abstract

At the center of Alzheimer's disease pathogenesis is the aberrant aggregation of amyloid-β (Aβ) into oligomers, fibrils and plaques. Effective monitoring of Aβ deposition directly in patients is essential to assist anti-Aβ therapeutics in target engagement and participant selection. In the advent of approved anti-Aβ therapeutics, biomarkers will become of fundamental importance in initiating treatments having disease modifying effects at the earliest stage. Two well-established Aβ biomarkers are widely utilized: Aβ-binding ligands for positron emission tomography and immunoassays to measure Aβ42 in cerebrospinal fluid. In this review, we will discuss the current clinical, diagnostic and research state of biomarkers for Aβ pathology. Furthermore, we will explore the current application of blood-based markers to assess Aβ pathology.

Head trauma in sports – clinical characteristics, epidemiology and biomarkers

“…Regarding the association of TBI with CTE, there are currently no validated fluid biomarkers for the disease, but AD‐type tau pathology may be detected using CSF total and phosphorylated tau . The best fluid biomarker for Aβ pathology (>90% accurate) is the CSF Aβ42/Aβ40 ratio, which appears to be working reasonably well in plasma as well . Recently, an intriguing interaction of greater RHI and increased microglial activation, as reflected by increased CSF levels of the soluble form of the triggering receptor expressed on myeloid cells 2 (sTREM2), with higher CSF total tau concentrations was reported in a sample of former professional American football players .…”

“…Regarding the association of TBI with CTE, there are currently no validated fluid biomarkers for the disease, but AD-type tau pathology may be detected using CSF total and phosphorylated tau [86]. The best fluid biomarker for Ab pathology (>90% accurate) is the CSF Ab42/Ab40 ratio, which appears to be working reasonably well in plasma as well [87].…”

Review: Fluid biomarkers for frontotemporal dementias

“…However, the overlap was large, which negates diagnostic usefulness on a case‐by‐case basis, and there were no significant correlations with cross‐sectional or longitudinal brain volume changes or disease duration . Recent data suggest that a reduced Aβ42/40 ratio in plasma reflects AD‐associated brain Aβ pathology with fair diagnostic accuracy (80‐90%) . Whether this could be used to exclude AD in FTD remains to be examined.…”

“…Combining the classical AD biomarkers (all normal) with NfL (increased) results in diagnostic sensitivities of 75-86% and specificities of 94-100% for FTD as compared to AD and cognitively normal controls [14]. In a more recent memory clinic-based study, CSF Ab42/40 (the most accurate Ab pathology fluid biomarker [40]) and T-tau/Ab42 ratios had high diagnostic utility in distinguishing AD from both bvFTD and semantic dementia (SD, sensitivities and specificities of 80-90%) [41]. Irrespective of subgroup (except logopenic variant primary progressive aphasia [lvPPA], which is associated with underlying AD pathology), FTD patients appeared to have a lower ratio of P-tau to T-tau in CSF [42].…”

Perspectives in fluid biomarkers in neurodegeneration from the 2019 biomarkers in neurodegenerative diseases course—a joint PhD student course at University College London and University of Gothenburg

“…Studies implementing novel techniques, such as mass spectrometry and ultrasensitive immunoassays, have shown promise in developing sensitive blood-based Aβ assays [14]. Plasma Aβ 42 measured using single molecule array (Simoa) technology was shown to be decreased in AD compared with controls and a ratio of plasma Aβ 42 / Aβ 40 was reduced in amyloid PET positive cases in a manner similar to CSF, but according to most studies, with greater overlap between Aβ-positive and Aβnegative patients [15,16].…”