Objective: Develop a cerebrospinal fluid biomarker signature for mild Alzheimer's disease (AD) in Alzheimer's Disease Neuroimaging Initiative (ADNI) subjects.Methods: Amyloid‐β 1 to 42 peptide (Aβ1–42), total tau (t‐tau), and tau phosphorylated at the threonine 181 were measured in (1) cerebrospinal fluid (CSF) samples obtained during baseline evaluation of 100 mild AD, 196 mild cognitive impairment, and 114 elderly cognitively normal (NC) subjects in ADNI; and (2) independent 56 autopsy‐confirmed AD cases and 52 age‐matched elderly NCs using a multiplex immunoassay. Detection of an AD CSF profile for t‐tau and Aβ1–42 in ADNI subjects was achieved using receiver operating characteristic cut points and logistic regression models derived from the autopsy‐confirmed CSF data.Results: CSF Aβ1–42 was the most sensitive biomarker for AD in the autopsy cohort of CSF samples: receiver operating characteristic area under the curve of 0.913 and sensitivity for AD detection of 96.4%. In the ADNI cohort, a logistic regression model for Aβ1–42, t‐tau, and APOε4 allele count provided the best assessment delineation of mild AD. An AD‐like baseline CSF profile for t‐tau/Aβ1–42 was detected in 33 of 37 ADNI mild cognitive impairment subjects who converted to probable AD during the first year of the study.Interpretation: The CSF biomarker signature of AD defined by Aβ1–42 and t‐tau in the autopsy‐confirmed AD cohort and confirmed in the cohort followed in ADNI for 12 months detects mild AD in a large, multisite, prospective clinical investigation, and this signature appears to predict conversion from mild cognitive impairment to AD. Ann Neurol 2009
In order to verify the potential association between the aetiopathogenesis of adolescent idiopathic scoliosis (AIS) and the process of sexual maturation, we determined the concentrations of oestrogens in pre- and postmenarcheal girls affected by this condition. AIS, occurring mostly in pubescent girls, is one of the most frequent forms of faulty posture. Therefore, it was assumed that the multifactorial pathomechanism of AIS involves significant deficiency of oestrogens. The diagnosis of AIS was established on the basis of physical examination and analyses of radiograms. Concentrations of FSH, LH, oestrogens, progesterone, osteocalcin and RANKL were determined by ELISA. The activity of alkaline phosphatase (AP) was measured by kinetic method. The study included pre- and postmenarcheal girls with AIS and corresponding groups of scoliosis-free controls. In premenarcheal scoliotic girls, the levels of FSH, LH and oestradiol were lower; the levels of progesterone, oestrone and oestriol were higher; and the concentrations of oestrone and oestriol were similar compared to premenarcheal controls. Higher levels of RANKL, osteocalcin and AP were observed in premenarcheal adolescents with AIS compared to controls. The concentrations of FSH, LH, oestradiol, and progesterone in postmenarcheal girls with scoliosis were lower, oestrone were slightly lower and oestriol did not differ compared with the control group. Significantly higher levels of RANKL, osteocalcin and AP were observed in postmenarcheal scoliotic adolescents compared with controls. There is an interdependence between the concentration of oestradiol and development of scoliosis. Determination of estradiol may have diagnostic value in the screening of spinal pathologies associated with AIS.
The best-studied biomarkers of Alzheimer's disease (AD) are the pathologically-linked cerebrospinal fluid (CSF) proteins amyloid-β 42 (Aβ1-42 ), total tau (t-tau), and tau phosphorylated on amino acid 181 (p-tau181 ). Many laboratories measure these
A cross-sectional study of 2 groups of patients with scoliosis, and an age-matched control group was conducted. Each of the groups such as patients with adolescent idiopathic scoliosis (AIS) as well as control group were divided additionally into 2 groups: premenarcheal and postmenarcheal girls. The aim of the study was to determine the levels of 25-OH-vitamin D3, calcium and phosphate, parathyroid hormone (PTH), and calcitonin in serum of pre- and postmenarcheal girls with AIS and corresponding groups of scoliosis-free controls. The primary etiology and pathogenesis of AIS remains unknown. It is assumed that vitamin D deficiency and genetic predisposition, for example, polymorphisms of vitamin D receptor, have a great significance. Vitamin D plays a key role in skeletal development and prevents bone atrophy, affects the absorption of calcium, maintains calcium-phosphate homeostasis, and the bone matrix mineralization. Its deficiency can result in a wide variety of skeletal deformities, low bone mass, and then leads to the disappearance of bone. Defects in trabecular bone structure and/or bone mineralization are the main features of scoliosis. Some studies have reported that Vitamin D deficiency is common among patients with AIS. The mechanism of Vitamin D action on scoliosis development is still unclear. Determination of serum 25-OH-D3 levels was performed using high-performance liquid chromatography chromatography; concentrations of calcium and phosphate were measured using colorimetric methods, and concentration of PTH and calcitonin was measured using ELISA system. Reduction in the serum levels of 25-OH-D3 and calcitonin in girls with AIS compared with healthy girls was demonstrated. The phosphate-calcium balance and PTH level seem to be normal in patients with AIS. The calcitonin level in girls with AIS is 2-fold lower than in healthy subjects. It is possible that the deficiency of vitamin D can be involved in AIS. 4.
9 September 2015 in Journal of Alzheimer’s Disease
Background: In previous studies, a dichotomous stratification of subjects into “cerebrospinal fluid (CSF) normal” and “CSF pathologic” was used to investigate the role of biomarkers in the prediction of progression to dementia in pre-dementia/mild c