[News on blood biomarker-based early diagnosis of the preliminary stages of Alzheimer's dementia].

Abstract

The early diagnosis of Alzheimer's disease (ADD) has gained new significance through the further discovery of blood biomarkers. Blood biomarkers are less expensive, can be measured fully automatically with high throughput, are less invasive and provide faster information on specific dementia biomarkers than current methods used in routine clinical practice such as amyloid positron emission tomography (PET) or CSF examination of underlying pathological changes in Alzheimer's disease (AD) in patients with cognitive impairment. The aim of this review is to provide a presentation of the added value of blood-based biomarkers for the early diagnosis of ADD. Individual blood biomarkers are presented regarding their diagnostic reliability and predictive value for the diagnosis of AD in precursors of ADD ranging from subjective cognitive impairment (SCD) to mild cognitive impairment (MCI). In addition, the revised criteria for the diagnosis and staging of AD are discussed. Markers of tau pathology such as a phosphorylated tau protein 217 (p-tau217), a phosphorylated tau protein 181 (p-tau181), a phosphorylated tau protein 231 (p-tau231), but also amyloid-β (Aβ) markers such as the ratio of Aβ1-42/ 1-40 are described as specific biomarkers for the early diagnosis of AD. In addition, new amyloid peptide ratios such as Aβ-3-42/-3-40 are discussed, which may provide more insights into the pathogenesis of AD, as this N-terminal elongated Aβ peptides are cleaved from the amyloid precursor protein via a biochemical oligodendroglia-dependent pathway (ADAMTS4=disintegrin and metalloproteinase with thrombospondin motifs 4), which is important in AD pathophysiology due to oligodendroglia involvement. In addition, new promising composite hybrid ratios are explained, which could provide advantages in the early diagnosis of AD, such as the AT217-term or the AT181-term, which relates Aβ1-40 to Aβ1-42 and multiplies it by p-tau217 and p-tau181, respectively. Overall, the review provides an overview of the potential of blood biomarkers in the early diagnosis of ADD. However, these biomarkers should not be used alone for early diagnosis, but should always be evaluated in conjunction with other tests such as cerebrospinal fluid analysis.