TY - JOUR

T1 - A Comprehensive Study of Alzheimer’s Disease Biomarkers in Plasma and Cerebrospinal Fluid

AU - Миночкин, Алесь Константинович

AU - Щербак, Сергей Григорьевич

AU - Лобзин, Владимир Юрьевич

AU - Коптева, Юлия Павловна

AU - Апалько, Светлана Вячеславовна

AU - Клиценко, Ольга Анатольевна

AU - Емелин, Андрей Юрьевич

PY - 2025/9/11

Y1 - 2025/9/11

N2 - Objectives. To determine, evaluate, and analyze the diagnostic value of various laboratory biomarkers of Alzheimer’s disease (AD) in the blood and cerebrospinal fluid (CSF). Materials and methods. The concentrations of 93 potential biomarkers in plasma and CSF were studied in a group of patients with AD at different stages (n = 53) and, separately, in a group at the predementia stage (n = 15). Results. Statistically significant correlations in different directions (p ≤ 0.05) were found between ratios characterizing the processes of amyloidosis and neurodegeneration (Aβ-42/Aβ-40, pTau181/Aβ-42, pTau181/tTau, and tTau/Aβ-42) on the one hand and markers associated with neuroinflammation, vascular pathology, angiogenesis, neuroimaging changes, and neuropsychological indicators on the other. Previous studies of markers associated with inflammation in CSF in AD have yielded quite different results and no marker has as yet been introduced into clinical practice. A significant number of biomarkers associated not only with the two classical pathogenetic links, but also with other pathophysiological processes, were identified. Conclusions. This work showed that use of CSF ratios (Aβ-42/Aβ-40, pTau181/Aβ-42, pTau181/tTau, and tTau/Aβ-42) reflecting the two main pathogenetic processes in AD is the most informative for verifying the two main components in the pathogenesis of the disease – amyloidogenesis and neurodegeneration. In the group of patients with amnestic mild cognitive impairment (aMCI), statistically significant relationships were demonstrated between neuroinflammation-associated cytokines, growth factors, complement system proteins, amyloidosis, and neurodegeneration-related ratios in CSF, PET, MRI, and neuropsychological tests, so these indicators can also be regarded as potential diagnostic biomarkers of the early stages, as well as possible predictors of conversion of MCI to dementia. Markers such as GFAP, apolipoprotein A1, GDF-15, IFN-γ, IL-5, IL-7, IL-8, IL-10, IL-12p70, IL-13, IL-17, VEGF, and complement C3 should be regarded as objects for continued future studies as biomarkers for early diagnosis.

AB - Objectives. To determine, evaluate, and analyze the diagnostic value of various laboratory biomarkers of Alzheimer’s disease (AD) in the blood and cerebrospinal fluid (CSF). Materials and methods. The concentrations of 93 potential biomarkers in plasma and CSF were studied in a group of patients with AD at different stages (n = 53) and, separately, in a group at the predementia stage (n = 15). Results. Statistically significant correlations in different directions (p ≤ 0.05) were found between ratios characterizing the processes of amyloidosis and neurodegeneration (Aβ-42/Aβ-40, pTau181/Aβ-42, pTau181/tTau, and tTau/Aβ-42) on the one hand and markers associated with neuroinflammation, vascular pathology, angiogenesis, neuroimaging changes, and neuropsychological indicators on the other. Previous studies of markers associated with inflammation in CSF in AD have yielded quite different results and no marker has as yet been introduced into clinical practice. A significant number of biomarkers associated not only with the two classical pathogenetic links, but also with other pathophysiological processes, were identified. Conclusions. This work showed that use of CSF ratios (Aβ-42/Aβ-40, pTau181/Aβ-42, pTau181/tTau, and tTau/Aβ-42) reflecting the two main pathogenetic processes in AD is the most informative for verifying the two main components in the pathogenesis of the disease – amyloidogenesis and neurodegeneration. In the group of patients with amnestic mild cognitive impairment (aMCI), statistically significant relationships were demonstrated between neuroinflammation-associated cytokines, growth factors, complement system proteins, amyloidosis, and neurodegeneration-related ratios in CSF, PET, MRI, and neuropsychological tests, so these indicators can also be regarded as potential diagnostic biomarkers of the early stages, as well as possible predictors of conversion of MCI to dementia. Markers such as GFAP, apolipoprotein A1, GDF-15, IFN-γ, IL-5, IL-7, IL-8, IL-10, IL-12p70, IL-13, IL-17, VEGF, and complement C3 should be regarded as objects for continued future studies as biomarkers for early diagnosis.

KW - Alzheimer’s disease

KW - Biomarkers

KW - Neurodegeneration

KW - Neuroinflammation

KW - Vascular growth factors

UR - https://www.mendeley.com/catalogue/b730b840-648d-3230-acf3-4f0b6b8962ca/

U2 - 10.1007/s11055-025-01881-1

DO - 10.1007/s11055-025-01881-1

M3 - Article

VL - 55

SP - 1216

EP - 1226

JO - Neuroscience and Behavioral Physiology

JF - Neuroscience and Behavioral Physiology

SN - 0097-0549

IS - 7

ER -